Miracle-dz/UniFAR-FTUs huggingface dataset:
Application of Velocity Gain Guidance to Far-Distance Rendezvous

Using impulse hypothesis to solve far-distance rendezvous is difficult to be realized in a real project and the guidance accuracy cannot be controlled. A two-maneuver guidance law is designed for the two-impulse rendezvous problem. The velocity gain guidance is applied to the first maneuver and the time-cut-off law is applied to the second one. Theoretical and simulation results show that the plan is credible. Accuracy requirements in far- distance rendezvous and in transform to close-in rendezous can be met.
A sharp interface immersed boundary method for solving flow with arbitrarily irregular and changing geometry

In this paper, a sharp interface immersed boundary method is developed for efficiently and robustly solving flow with arbitrarily irregular and changing geometries. The proposed method employs a three-step prediction-correction flow reconstruction scheme for boundary treatment and enforces Dirichlet, Neumann, Robin, and Cauchy boundary conditions in a straightforward and consistent manner. Numerical experiments concerning flow of two and three space dimensions, stationary and moving objects, convex and concave geometries, no-slip and slip wall boundary conditions are conducted to demonstrate the proposed method.
A Rab6 to Rab11 transition is required for dense-core granule and exosome biogenesis in Drosophila secondary cells

Secretory cells in glands and the nervous system frequently package and store proteins destined for regulated secretion in dense-core granules (DCGs), which disperse when released from the cell surface. Despite the relevance of this dynamic process to diseases such as diabetes and human neurodegenerative disorders, our mechanistic understanding is relatively limited, because of the lack of good cell models to follow the nanoscale events involved. Here, we employ the prostate-like secondary cells (SCs) of the Drosophila male accessory gland to dissect the cell biology and genetics of DCG biogenesis. These cells contain unusually enlarged DCGs, which are assembled in compartments that also form secreted nanovesicles called exosomes. We demonstrate that known conserved regulators of DCG biogenesis, including the small G-protein Arf1 and the coatomer complex AP-1, play key roles in making SC DCGs. Using real-time imaging, we find that the aggregation events driving DCG biogenesis are accompanied by a change in the membrane associated small Rab GTPases which are major regulators of membrane and protein trafficking in the secretory and endosomal systems. Indeed, a transition from trans-Golgi Rab6 to recycling endosomal protein Rab11, which requires conserved DCG regulators like AP-1, is essential for DCG and exosome biogenesis. Our data allow us to develop a model for DCG biogenesis that brings together several previously disparate observations concerning this process and highlights the importance of communication between the secretory and endosomal systems in controlling regulated secretion. Author summary Cells communicate with each other by releasing signalling molecules that bind receptors on target cells and alter their behaviour. Before their release, these signals are typically stored in condensed structures called dense-core granules (DCGs). DCGs are found in many animal species and their dysregulation is linked to several major human diseases, such as diabetes and neurodegenerative disorders. However, the mechanisms controlling DCG formation and secretion are only partly understood. Here we study this process in fruit flies using a secretory cell, which contains unusually large DCGs. We show that known regulators of DCG formation in mammals also control DCG production in these fly cells and identify new DCG assembly steps by following the process in living cells. Furthermore, we show that the cell’s secretory and recycling endosomal compartments must interact to induce the rapid condensation of proteins into a DCG, and that known regulators of DCG formation are needed for this crucial event to take place. Our work provides a platform from which to work out the molecular mechanisms that enable this critical secretory-endosomal interaction and probe its roles in diseases of secretion.
Super-resolution mapping of anisotropic tissue structure with diffusion MRI and deep learning

Diffusion magnetic resonance imaging (diffusion MRI) is widely employed to probe the diffusive motion of water molecules within the tissue. Numerous diseases and processes affecting the central nervous system can be detected and monitored via diffusion MRI thanks to its sensitivity to microstructural alterations in tissue. The latter has prompted interest in quantitative mapping of the microstructural parameters, such as the fiber orientation distribution function (fODF), which is instrumental for noninvasively mapping the underlying axonal fiber tracts in white matter through a procedure known as tractography. However, such applications demand repeated acquisitions of MRI volumes with varied experimental parameters demanding long acquisition times and/or limited spatial resolution. In this work, we present a deep-learning-based approach for increasing the spatial resolution of diffusion MRI data in the form of fODFs obtained through constrained spherical deconvolution. The proposed approach is evaluated on high quality data from the Human Connectome Project, and is shown to generate upsampled results with a greater correspondence to ground truth high-resolution data than can be achieved with ordinary spline interpolation methods.
Disruption of a BTB-ZF transcription factor causes female sterility and melanization in the larval body of the silkworm, Bombyx mori

The dilute black (bd) of the silkworm Bombyx mori is a recessive mutant that produces a grayish-black color in the larval integument, instead of the characteristic white color found in wild-type larvae. In addition, eggs produced by bd females are sterile due to a deficiency in the micropylar apparatus. We identified candidate genes responsible for the bd phenotype using publicly available RNA-seq data. One of these candidate genes was homologous to the maternal gene required for meiosis (mamo) of Drosophila melanogaster, which encodes a broad-complex, tramtrack, and bric-à-brac-zinc finger (BTB-ZF) transcription factor essential for female fertility. In three independent bd strains, the expression of the B. mori mamo (Bmmamo) was downregulated in the larval integument. Using a CRISPR/Cas9-mediated knockout strategy, we found that Bmmamo knockout mutants exhibit a grayish-black color in the larval integument and female infertility. Moreover, larvae obtained from the complementation cross between bd/+ mutants and heterozygous knockouts for the Bmmamo also exhibited a grayish-black color, indicating that Bmmamo is responsible for the bd phenotype. Gene expression analysis using Bmmamo knockout mutants suggested that the BmMamo protein suppresses the expression of melanin synthesis genes. Previous comparative genome analysis revealed that the Bmmamo was selected during silkworm domestication, and we found that Bmmamo expression in the larval integument is higher in B. mori than in the wild silkworm B. mandarina, suggesting that the Bmmamo is involved in domestication-associated pigmentation changes of the silkworm. Graphical Abstract
Analytical solutions for the short-term plasticity

Synaptic dynamics plays a key role in neuronal communication. Due to its high-dimensionality, the main fundamental mechanisms triggering different synaptic dynamics and its relation with the neurotransmitters release regimes (facilitation, biphasic, and depression) are still elusive. For a general set of parameters, and by means of an approximated solution for a set of differential equations associated with a synaptic model, we obtain a discrete map that provides analytical solutions that shed light into the dynamics of synapses. Assuming that the presynaptic neuron perturbing the neuron whose synapse is being modelled is spiking periodically, we derive the stable equilibria and the maximal values for the release regimes as a function of the percentage of neurotransmitter released and the mean frequency of the presynaptic spiking neuron. Assuming that the presynaptic neuron is spiking stochastically following a Poisson distribution, we demonstrate that the equations for the time average of the trajectory are the same as the map under the periodic presynaptic stimulus, admitting the same equilibrium points. Thus, the synapses under stochastic presynaptic spikes, emulating the spiking behaviour produced by a complex neural network, wander around the equilibrium points of the synapses under periodic stimulus, which can be fully analytically calculated. Author summary Based on the model proposed by Tsodyks et al., we obtained a map approximation to study analytically the dynamics of short-term synaptic plasticity. We identified the synaptic regimes named facilitation, depression, and biphasic in the parameters space, and determined the maximal and equilibrium points of active neurotransmitters for presynaptic neurons spiking periodically and stochastically following a Poisson process. Besides that, we verify that the time average of the variables for the synaptic dynamics driven by presynaptic neurons spiking following a Poisson distribution presents the equilibrium points obtained for the synaptic driven by periodic presynaptic neurons, spiking with a frequency that is the mean frequency of the Poisson distribution. These results shed analytical light into the understanding of synaptic dynamics.
The impact of hearing loss on cognitive impairment: The mediating role of depressive symptoms and the moderating role of social relationships

Background Given the potentially negative effects of hearing loss on mental health and cognitive function, it is critical to gain a better understanding of the mechanisms underlying the link between hearing loss and cognitive impairment. This study aimed to investigate the moderating effects of social relationships, including their components in the role of depressive symptoms as a mediator between hearing loss and cognitive impairment. Methods Cross-sectional analyses were conducted with 8,094 Chinese older adults (aged ≥65 years) from the Chinese Longitudinal Healthy Longevity Survey in 2018. Simple mediation analysis and moderated mediation analysis were conducted to examine the roles of depressive symptoms and social relationships in the association between hearing loss and cognitive impairment. Results There is a significant correlation between hearing loss, depressive symptoms, social relationships, and cognitive function. Depressive symptoms partially mediated the association between hearing loss and cognitive function [standardized regression B-coefficient (B) = −0.114; 95% confidence interval (CI): (−0.158, −0.076)]. Social relationships moderated the effect of hearing loss on cognitive function through both path b (depressive symptoms - cognitive function) [B = 0.021; 95% CI: (0.008, 0.034)], and path c’ (hearing loss-cognitive function) [B = 0.597; 95% CI: (0.463, 0.730)]. Furthermore, social activities and social networks moderated both the direct and indirect effects of moderated mediation. However, there appeared to be no moderated effect of social support for both the direct and indirect paths. Conclusion Social relationships moderated both the direct and indirect effects of depressive symptoms on the association between hearing loss and cognitive impairment. These findings shed light on the mechanisms underlying the relationship between hearing loss and cognitive impairment in Chinese older adults. It might be worthwhile to recommend multidimensional health and social interventions aimed at improving mental health and social inclusion among older adults with hearing loss.
Use of gene therapy for optic nerve protection: Current concepts

Gene therapy has become an essential treatment for optic nerve injury (ONI) in recent years, and great strides have been made using animal models. ONI, which is characterized by the loss of retinal ganglion cells (RGCs) and axons, can induce abnormalities in the pupil light reflex, visual field defects, and even vision loss. The eye is a natural organ to target with gene therapy because of its high accessibility and certain immune privilege. As such, numerous gene therapy trials are underway for treating eye diseases such as glaucoma. The aim of this review was to cover research progress made in gene therapy for ONI. Specifically, we focus on the potential of gene therapy to prevent the progression of neurodegenerative diseases and protect both RGCs and axons. We cover the basic information of gene therapy, including the classification of gene therapy, especially focusing on genome editing therapy, and then we introduce common editing tools and vector tools such as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) -Cas9 and adeno-associated virus (AAV). We also summarize the progress made on understanding the roles of brain derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), phosphatase-tensin homolog (PTEN), suppressor of cytokine signal transduction 3 (SOCS3), histone acetyltransferases (HATs), and other important molecules in optic nerve protection. However, gene therapy still has many challenges, such as misalignment and mutations, immunogenicity of AAV, time it takes and economic cost involved, which means that these issues need to be addressed before clinical trials can be considered.
Understanding the mode of action of AgroGain®, a biostimulant derived from the red seaweed Kappaphycus alvarezii in the stimulation of cotyledon expansion and growth of Cucumis sativa (cucumber)

Seaweed-based biostimulants are sustainable agriculture inputs that are known to have a multitude of beneficial effects on plant growth and productivity. This study demonstrates that Agrogain® (Product code: LBS6), a Kappaphycus alvarezii-derived biostimulant induced the expansion of cucumber cotyledons. Seven days treatment of LBS6-supplementation showed a 29.2% increase in area of expanded cotyledons, as compared to the control. LBS6-treated cotyledons also showed higher amylase activity, suggesting starch to sucrose conversion was used efficiently as an energy source during expansion. To understand the mechanisms of LBS6-induced expansion, real time gene expression analysis was carried out. This revealed that LBS6-treated cotyledons differentially modulated the expression of genes involved in cell division, cell number, cell expansion and cell size. LBS6 treatment also differentially regulated the expression of those genes involved in auxin and cytokinin metabolism. Further, foliar application of LBS6 on cucumber plants being grown under hydroponic conditions showed improved plant growth as compared to the control. The total leaf area of LBS6-sprayed plants increased by 19.1%, as compared to control. LBS6-sprayed plants efficiently regulated photosynthetic quenching by reducing loss via non-photochemical and non-regulatory quenching. LBS6 applications also modulated changes in the steady-state photosynthetic parameters of the cucumber leaves. It was demonstrated that LBS6 treatment modulated the electron and proton transport related pathways which help plants to efficiently utilize the photosynthetic radiation for optimal growth. These results provide clear evidence that bioactive compounds present in LBS6 improved the growth of cucumber plants by regulating the physiological as well as developmental pathways.
Modeling and numerical analysis for mechanical characterization of soft tissue mechanism applying inverse finite element technique

Tissue-mimicking materials [e.g., polyvinyl alcohol cryogel (PVA-C)] are extensively used in clinical applications such as tissue repair and tissue engineering. Various mechanical testing techniques have been used to assess the biomechanical compatibility of tissue-mimicking materials. This article presents the development of inverse finite element (FE) techniques that are solved using numerical optimization to characterize the mechanical properties of PVA-C specimens. In this study, a numerical analysis where the displacement influence factor was employed in conjunction with a linear elastic model of finite thickness was performed. In the analysis, the effects of Poisson's ratio, specimen aspect ratio, and relative indentation depth were investigated, and a novel mathematical term was introduced to Sneddon's equation. In addition, a robust optimization algorithm was developed in MATLAB that utilized FE modeling for parameter estimation before it was rigorously validated.
DeepDixon synthetic CT for [18F]FET PET/MRI attenuation correction of post-surgery glioma patients with metal implants

Purpose Conventional magnetic resonance imaging (MRI) can for glioma assessment be supplemented by positron emission tomography (PET) imaging with radiolabeled amino acids such as O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET), which provides additional information on metabolic properties. In neuro-oncology, patients often undergo brain and skull altering treatment, which is known to challenge MRI-based attenuation correction (MR-AC) methods and thereby impact the simplified semi-quantitative measures such as tumor-to-brain ratio (TBR) used in clinical routine. The aim of the present study was to examine the applicability of our deep learning method, DeepDixon, for MR-AC in [18F]FET PET/MRI scans of a post-surgery glioma cohort with metal implants. Methods The MR-AC maps were assessed for all 194 included post-surgery glioma patients (318 studies). The subgroup of 147 patients (222 studies, 200 MBq [18F]FET PET/MRI) with tracer uptake above 1 ml were subsequently reconstructed with DeepDixon, vendor-default atlas-based method, and a low-dose computed tomography (CT) used as reference. The biological tumor volume (BTV) was delineated on each patient by isocontouring tracer uptake above a TBR threshold of 1.6. We evaluated the MR-AC methods using the recommended clinical metrics BTV and mean and maximum TBR on a patient-by-patient basis against the reference with CT-AC. Results Ninety-seven percent of the studies (310/318) did not have any major artifacts using DeepDixon, which resulted in a Dice coefficient of 0.89/0.83 for tissue/bone, respectively, compared to 0.84/0.57 when using atlas. The average difference between DeepDixon and CT-AC was within 0.2% across all clinical metrics, and no statistically significant difference was found. When using DeepDixon, only 3 out of 222 studies (1%) exceeded our acceptance criteria compared to 72 of the 222 studies (32%) with the atlas method. Conclusion We evaluated the performance of a state-of-the-art MR-AC method on the largest post-surgical glioma patient cohort to date. We found that DeepDixon could overcome most of the issues arising from irregular anatomy and metal artifacts present in the cohort resulting in clinical metrics within acceptable limits of the reference CT-AC in almost all cases. This is a significant improvement over the vendor-provided atlas method and of particular importance in response assessment.
Effectiveness and safety of capecitabine, irinotecan and panitumumab in advanced colorectal cancer

Introduction Capecitabine, irinotecan, and panitumumab (CAPIRI-P) is a controversial regimen for metastatic colorectal cancer, with concerns regarding the efficacy and toxicity. However, its toxicity profile has been improved with dose reduction, and concerns regarding efficacy have been extrapolated from other trials. This retrospective study reports the real-world effectiveness and safety of modified CAPIRI-P (mCAPIRI-P). Material and methods Advanced colorectal cancer patients receiving mCAPIPI-P in the first-line setting between July 2019 and December 2021 were analyzed. The progression-free survival on treatment (PFSOT) and overall survival (OS) were estimated using the Kaplan–Meier method, and the association with clinical and disease factors was analyzed using the Cox regression model. Serial changes in carcinoembryonic antigen (CEA) level and treatment toxicity were also evaluated. Results A total of 106 patients were included, of whom 97 (92%) and 31 (29%) had left-sided primary and unresectable liver-only disease, respectively. The median PFSOT and OS were 15.4 (95% CI 12.5–18.3) and 25.5 (95% CI 17.6–33.4) months, respectively. Sixteen (51.6%) and 10 (32.3%) liver-only disease patients underwent secondary liver treatment and R0 resection, respectively. In multivariable Cox regression, CEA responders (PFSOT: HR 0.53) and CEA normalization (PFSOT: HR 0.27; OS: HR 0.28) were independent favorable prognostic factors for PFSOT and OS. Grade ≥3 toxicity rate was 43%, mainly related to uncomplicated hematological toxicities. Conclusion The real-world data show that mCAPIRI-P is safe and effective as the first-line treatment regimen for RAS wild-type advanced colorectal cancer and warrants further study.
Satisfaction with care quality and anxiety among family members during nursing home visiting restrictions: The chain mediating effect of emotional regulation and perceived stress

Introduction This study aimed to investigate the psychological well-being (perceived stress and anxiety) of Chinese family members during nursing home visiting restrictions and to elucidate the relationships among satisfaction with care quality, emotion regulation, perceived stress, and anxiety. Methods An online survey was conducted with a cross-sectional study design. From 18 to 29 January 2022, a total of 571 family members of nursing home residents completed online questionnaires comprising socio-demographic characteristics, satisfaction with care quality, emotion regulation, perceived stress, and anxiety. Mediation analyses were performed to estimate the direct and indirect effects of satisfaction with care quality on anxiety using the PROCESS macro for SPSS. Results The results showed that approximately one-quarter of Chinese family members had anxiety symptoms during nursing home visiting restrictions. Satisfaction with care quality affected anxiety via three mediating paths: (a) through cognitive reappraisal (effect = 0.028); (b) through cognitive reappraisal and perceived stress sequentially (effect = −0.057); and (c) through perceived stress (effect = −0.212). The chain mediating effect (path b) accounted for 23.7% of the total effect. Conclusions These findings corroborated our hypothesis that cognitive reappraisal (a kind of emotion regulation strategy) and perceived stress mediated the relationship between satisfaction with care quality and anxiety during nursing home visiting restrictions. Efforts to address family members’ psychological well-being by focusing on cognitive reappraisal should be considered.