Monocytes Release Pro-Cathepsin D to Drive Blood-to-Brain Transcytosis in Diabetes.

BACKGROUND: Microvascular complications are the major outcome of type 2 diabetes progression, and the underlying mechanism remains to be determined. METHODS: High-throughput RNA sequencing was performed using human monocyte samples from controls and diabetes. The transgenic mice expressing human CTSD (cathepsin D) in the monocytes was constructed using CD68 promoter. In vivo 2-photon imaging, behavioral tests, immunofluorescence, transmission electron microscopy, Western blot analysis, vascular leakage assay, and single-cell RNA sequencing were performed to clarify the phenotype and elucidate the molecular mechanism. RESULTS: Monocytes expressed high-level CTSD in patients with type 2 diabetes. The transgenic mice expressing human CTSD in the monocytes showed increased brain microvascular permeability resembling the diabetic microvascular phenotype, accompanied by cognitive deficit. Mechanistically, the monocytes release nonenzymatic pro-CTSD to upregulate caveolin expression in brain endothelium triggering caveolae-mediated transcytosis, without affecting the paracellular route of brain microvasculature. The circulating pro-CTSD activated the caveolae-mediated transcytosis in brain endothelial cells via its binding with low-density LRP1 (lipoprotein receptor-related protein 1). Importantly, genetic ablation of CTSD in the monocytes exhibited a protective effect against the diabetes-enhanced brain microvascular transcytosis and the diabetes-induced cognitive impairment. CONCLUSIONS: These findings uncover the novel role of circulatory pro-CTSD from monocytes in the pathogenesis of cerebral microvascular lesions in diabetes. The circulatory pro-CTSD is a potential target for the intervention of microvascular complications in diabetes.

Void Volume Fraction of Granular Scaffolds.

Void volume fraction (VVF) is a global measurement frequently used to characterize the void space of granular scaffolds, yet there is no gold standard by which to measure VVF in practice. To study the relationship  between VVF and particles of varying size, form, and composition, a library of 3D simulated scaffolds is used. Results reveal that relative to particle count, VVF is a less predictable metric across replicate scaffolds. Simulated scaffolds are used to explores the relationship between microscope magnification and VVF, and recommendations are offered for optimizing the accuracy of approximating VVF using 2D microscope images. Lastly, VVF of hydrogel granular scaffolds is measured while varying four input parameters: image quality, magnification, analysis software, and intensity threshold. Results show that VVF is highly sensitive to these parameters. Overall, random packing produces variation in VVF among granular scaffolds comprising the same particle populations. Furthermore, while VVF is used to compare the porosity of granular materials within a study, VVF is a less reliable metric across studies that use different input parameters. VVF, a global measurement, cannot describe the dimensions of porosity within granular scaffolds, and the work supports the notion that more descriptors are necessary to sufficiently characterize void space.

Annular illumination in 2D quantitative phase imaging: a systematic evaluation.

Quantitative phase imaging (QPI) is an invaluable microscopic technology for definitively imaging phase objects such as biological cells and optical fibers. Traditionally, the condenser lens in QPI produces disk illumination of the object. However, it has been realized by numerous investigators that annular illumination can produce higher-resolution images. Although this performance improvement is impressive and well documented, the evidence presented has invariably been qualitative in nature. Recently, a theoretical basis for annular illumination was presented by Bao et al. [Appl. Opt.58, 137 (2019)APOPAI0003-693510.1364/AO.58.000137]. In our current work, systematic experimental QPI measurements are made with a reference phase mask to rigorously document the performance of annular illumination. In both theory and experiment, three spatial-frequency regions are identified: low, mid, and high. The low spatial-frequency region response is very similar for disk and annular illumination, both theoretically and experimentally. Theoretically, the high spatial-frequency region response is predicted to be much better for the annular illumination compared to the disk illumination--and is experimentally confirmed. In addition, the mid-spatial-frequency region response is theoretically predicted to be less for annular illumination than for disk illumination. This theoretical degradation of the mid-spatial-frequency region is only slightly experimentally observed. This bonus, although not well understood, further elevates the performance of annular illumination over disk illumination.

Analytical phase optical transfer function for Gaussian illumination and the optimized illumination profiles.

The imaging performance of tomographic deconvolution phase microscopy can be described in terms of the phase optical transfer function (POTF) which, in turn, depends on the illumination profile. To facilitate the optimization of the illumination profile, an analytical calculation method based on polynomial fitting is developed to describe the POTF for general nonuniform axially symmetric illumination. This is then applied to Gaussian and related profiles. Compared to numerical integration methods that integrate over a series of annuli, the present analytical method is much faster and is equally accurate. Further, a "balanced distribution" criterion for the POTF and a least-squares minimization are presented to optimize the uniformity of the POTF. An optimum general profile is found analytically by relaxed optimal search, and an optimum Gaussian profile is found through a tree search. Numerical simulations confirm the performance of these optimum profiles and support the balanced distribution criterion introduced.

Risk Factors of Psychological Responses of Chinese University Students During the COVID-19 Outbreak: Cross-sectional Web-Based Survey Study.

BACKGROUND: COVID-19 is a highly contagious and highly pathogenic disease caused by a novel coronavirus, SARS-CoV-2, and it has become a pandemic. As a vulnerable population, university students are at high risk during the epidemic, as they have high mobility and often overlook the severity of the disease because they receive incomplete information about the epidemic. In addition to the risk of death from infection, the epidemic has placed substantial psychological pressure on the public. In this respect, university students are more prone to psychological problems induced by the epidemic compared to the general population because for most students, university life is their first time outside the structure of the family, and their mental development is still immature. Internal and external expectations and academic stress lead to excessive pressure on students, and unhealthy lifestyles also deteriorate their mental health. The outbreak of COVID-19 was a significant social event, and it could potentially have a great impact on the life and the mental health of university students. Therefore, it is of importance to investigate university students' mental health status during the outbreak of COVID-19. OBJECTIVE: The principal objective of this study was to investigate the influencing factors of the psychological responses of Chinese university students during the COVID-19 outbreak. METHODS: This study used data from a survey conducted in China between February 21 and 24, 2020, and the data set contains demographic information and psychological measures including the Self-Rating Anxiety Scale, the Self-Rating Depression Scale, and the compulsive behaviors portion of the Yale-Brown Obsessive-Compulsive Scale. A total of 2284 questionnaires were returned, and 2270 of them were valid and were used for analysis. The Mann-Whitney U test for two independent samples and binary logistic regression models were used for statistical analysis. RESULTS: Our study surveyed 563 medical students and 1707 nonmedical students. Among them, 251/2270 students (11.06%) had mental health issues. The results showed that contact history of similar infectious disease (odds ratio [OR] 3.363, P=.02), past medical history (OR 3.282, P<.001), and compulsive behaviors (OR 3.525, P<.001) contributed to the risk of mental health issues. Older students (OR 0.928, P=.02), regular daily life during the epidemic outbreak (OR 0.410, P<.001), exercise during the epidemic outbreak (OR 0.456, P<.001), and concern related to COVID-19 (OR 0.638, P=.002) were protective factors for mental health issues. CONCLUSIONS: According to the study results, mental health issues have seriously affected university students, and our results are beneficial for identifying groups of university students who are at risk for possible mental health issues so that universities and families can prevent or intervene in the development of potential mental health issues at the early stage of their development.

Three-dimensional phase optical transfer function in axially symmetric microscopic quantitative phase imaging.

Three-dimensional quantitative phase imaging (3D QPI) is widely recognized as a potentially high-impact microscopic modality. Central to determining the resolution capability of 3D QPI is the phase optical transfer function (POTF). The magnitude of the POTF over its spatial frequency coverage (SFC) specifies the intensity of the response for each allowed spatial frequency. In this paper, a detailed analysis of the POTF for an axially symmetric optical configuration is presented. First, a useful geometric interpretation of the SFC, which enables its visualization, is presented. Second, a closed-form 1D integral expression is derived for the POTF in the general nonparaxial case, which enables rapid calculation of the POTF. Third, this formulation is applied to disk, annular, multi-annuli, and Gaussian illuminations as well as to an annular objective. Taken together, these contributions enable the visualization and simplified calculation of the 3D axially symmetric POTF and provide a basis for optimizing QPI in a wide range of applications.

Is the relationship between social support and depressive symptoms mediated by hope among Chinese central nervous system tumor patients?

BACKGROUND: It is common for central nervous system (CNS) tumor patients to suffer from depressive symptoms. If unrecognized or untreated, CNS tumors may lead to many serious problems in these patients. This study examines the association of social support with depressive symptoms in CNS tumor patients and explores the extent to which hope mediates this relationship. METHODS: A total of 269 CNS tumor patients in China were included in this study. We assessed depressive symptoms using the Epidemiologic Studies Depression Scale (CES-D), social support using the Perceived Social Support Scale (PSSS), and hope using the Herth Hope Index (HHI). Questionnaires were distributed to collect these data. Hierarchical linear regression analyses explored the interrelationship between social support, hope, and depressive symptoms. RESULTS: After adjustment for demographic characteristics, patients with less social support exhibited more depressive symptoms (ß = - 0.452, P < 0.01). Social support explained 19.1% of the variance in depressive symptoms. After adding hope to the regression model, the effect size for social support was reduced by over half but remained significant (from ß = - 0.452 to ß = - 0.218, P < 0.01). In addition, a lower level of hope (ß = - 0.386, P < 0.01) was associated with more depressive symptoms, and this measure explained an additional 9.3% of the variance in depressive symptoms. CONCLUSIONS: Much of the relationship between social support and depressive symptoms is explained by hope. Thus, interventions boosting both social support and hope help to reduce depressive symptoms in patients with CNS tumors.

Two improved defocus quantitative phase imaging methods: discussion.

Multifilter phase imaging with partially coherent light (MFPI-PC) and phase optical transfer function recovery (POTFR) are two viable defocus-based, two-dimensional quantitative phase imaging (QPI) methods. While both methods use transfer function inversion, MFPI-PC is based on the in-focus intensity derivative, while POTFR is based on the intensity difference between symmetrically defocused images. This paper compares and contrasts MFPI-PC and POTFR. Six disadvantages (five in MFPI-PC and one in POTFR) are identified. Improvement strategies to overcome each of the six shortcomings are identified and implemented, and both methods are shown to be clearly improved. The revised MFPI-PC is shown to be more accurate than the original MFPI-PC and generally more accurate than the revised POTFR. The revised POTFR is shown to be inherently faster than the original POTFR and also slightly faster than the revised MFPI-PC.

Weighted-least-squares multi-filter phase imaging with partially coherent light: characteristics of annular illumination.

Multi-filter phase imaging with partially coherent light (MFPI-PC) is a promising microscopic quantitative phase imaging (QPI) method that measures the phase of a transparent object. In the present work, a weighted-least-squares version is developed and applied to the important case of annular illumination. The resulting improved algorithms have largely solved the noise magnification problem associated with the original MFPI-PC in annular illumination. Simulation and microlens experiments are used to validate the new QPI method for the case of annular illumination.

Iterative optimization in tomographic deconvolution phase microscopy.

Tomographic deconvolution phase microscopy (TDPM) is a three-dimensional (3D) quantitative phase imaging (QPI) method using partially coherent light that can be implemented on a commercial microscope platform. However, the measurement procedure is relatively time-consuming because it requires many illumination angles. In the present work, an edge-preserving iterative optimization algorithm is presented and applied to TDPM, so that the required number of illumination angles is reduced from 15 to 3, while the measurement accuracy remains high. In addition, the iterative algorithm does not require matrix representation of operators, so the memory requirement is correspondingly reduced.

Quantitative phase imaging of fiber Bragg gratings in multicore fibers.

Fiber Bragg gratings (FBGs) and multi-core fibers (MCFs) have independently demonstrated high levels of performance in numerous diverse applications. When integrated together, the devices can offer enhanced performance as well as open more applications. In all of these cases, the refractive index (RI) characterization of the FBGs is crucial in monitoring and validating the fabricated devices. To accomplish this, quantitative phase imaging (QPI) is a promising RI characterization candidate satisfying all of the requirements: noninvasive measurement, quantitative characterization, sub-micrometer resolution, no a priori knowledge, and 3D reconstruction. In this paper, we propose a new QPI method for characterization of the RI distribution of multiple FBGs in a single MCF. We have identified the key challenges associated with this approach: the pixel integration effect, aliasing effect, numerical aperture requirement, and characteristic functions recovery. We have further identified approaches for overcoming each of these challenges that have previously impeded this direction of research. The proposed method is supported by simulations of 2D and 3D gratings.

"Five-layer gasket seal" watertight closure for reconstruction of the skull base in complex bilateral traumatic intraorbital meningoencephaloceles: a case report and literature review.

PURPOSE: Traumatic meningoencephalocele primarily occurs as a rare but complex complication of cranial base and orbital roof fractures. Traumatic intraorbital meningoencephalocele, which is rare and easily overlooked, can be life-threatening since cephalomeningitis occurs due to cerebrospinal fluid (CSF) leakage. It is obscure for the operative indications or standard surgical methods of traumatic meningoencephaloceles since the combined intricate craniofacial and basal fractures, brain injury, and CSF leak may exist. This case report proposes a new operative method for the repair of complex skull base fractures following traumatic intraorbital meningoencephalocele. METHODS: A 30-year-old male with a history of complex trauma presented with symptoms of exophthalmos and traumatic CSF rhinorrhea was evaluated via 3D CT of the skull base and brain MRI and was diagnosed with bilateral intraorbital meningoencephaloceles and multiple craniofacial bone, skull base, and orbit fractures. RESULTS: Successful resection of the meningoencephaloceles and reconstruction of the skull base defects were performed via craniotomy using a "five-layer gasket seal" technique that involved, from extracranial to intracranial, a gelatin sponge, muscular paste, vascularized periosteum, RapidSorb Orbital Floor Plate (OrbFloor), and Neuro-Patch layers. CONCLUSIONS: The diagnosis and treatment of complex intraorbital meningoencephalocele require careful attention. Resection of herniated tissue is suggested due to potential contamination. The "five-layer gasket seal" watertight closure technique is recommended for successful repair of the skull base in cases involving traumatic meningoencephalocele with complex skull base fractures.

Prevalence and associated positive psychological variables of anxiety and depression among patients with central nervous system tumors in China: a cross-sectional study.

BACKGROUND: Anxiety and depression have been identified as common psychological distresses faced by the majority of patients with cancer. However, no studies have investigated the relationship between positive psychological variables (hope, optimism and general self-efficacy) and anxiety and depression among patients with central nervous system (CNS) tumors in China. Our hypothesis is that the patients with higher levels of hope, optimism or general self-efficacy have lower levels of anxiety and depression when encountered by stressful life events such as CNS tumors. METHODS: Questionnaires, including the Hospital Anxiety and Depression Scale, the Herth Hope Index, the Life Orientation Scale-Revised and the General Self-Efficacy Scale, and demographic and clinical records were used to collect information about patients with CNS tumors in Liaoning Province, China. The study included 222 patients (effective response rate: 66.1%). Hierarchical linear regression analyses were performed to explore the associations among hope, optimism, general self-efficacy and anxiety/depression. RESULTS: Prevalence of anxiety and depression were 42.8 and 32.4%, respectively, among patients with CNS tumors. Hope and optimism both were negatively associated with anxiety and together accounted for 21.4% of variance in anxiety. Similarly, hope and optimism both were negatively associated with depression and accounted for 32.4% of variance in depression. CONCLUSIONS: The high prevalence of anxiety and depression among patients with CNS tumors should receive more attention in Chinese medical settings. To help reduce anxiety and depression, health care professionals should develop interventions to promote hope and optimism based on patients' specific needs.

Clarification and unification of the obliquity factor in diffraction and scattering theories: discussion.

Two-dimensional (2D) and three-dimensional (3D) diffraction theories form the underlying basis of quantitative phase imaging. This paper reviews how 2D and 3D diffraction theories are developed based on thin and thick object requirements. However, some previously reported work has mixed 2D and 3D theories. This discussion shows that it is possible to enable consistent mixed use of 2D and 3D theories by applying appropriate obliquity factor (OF) modifications. The discussion is concluded with an overall unifying representation for the usage of the OF modifications in 2D and 3D diffraction theories as applied to both thin and thick objects.

Quantitative phase imaging method based on an analytical nonparaxial partially coherent phase optical transfer function: erratum.

A correction is given for Eq. (8) in J. Opt. Soc. Am. A33, 2125 (2016)JOAOD60740-323210.1364/JOSAA.33.002125.

The uncinate fasciculus as observed using diffusion spectrum imaging in the human brain.

INTRODUCTION: The definitive structure and comprehensive role of the uncinate fasciculus (UF) are still obscure. We aimed to map the human UF white matter tractography and investigate the asymmetry, connectivity, and segmentation of the UF. METHODS: Subcomponents of the UF were analyzed in 9 normal subjects and a 30-subject diffusion spectrum imaging (DSI) template (CMU-30). DSI and microdissection were performed to explore the tractography of the UF. RESULTS: Both methods revealed that it connects the anterior part of the temporal lobe (superior temporal gyrus and temporal pole) with the inferior frontal cortex and the orbitofrontal cortex. The UF starts at the temporal gyrus, runs inferiorly to the inferior frontal occipital fasciculus and splits into two branches, terminating in the ventrolateral frontal cortex and the rostral middle frontal cortex. Our study showed that the cortical areas of termination in the frontal lobe of the UF are the pars triangularis and pars orbitalis. The relative volume of the UF in both hemispheres was calculated. An independent t test was used to determine variances in the value of tract volume between the left and right hemispheres. The volume and the length showed a significant statistical difference in the total volume of the UF. We suggest the UF is leftward asymmetry. CONCLUSIONS: The two parts of the UF were divided, but the conclusion is not consistent with the previous published articles which have shown that the UF is segmented into three parts. Our research facilitates a better understanding of the UF.

Quantitative phase imaging method based on an analytical nonparaxial partially coherent phase optical transfer function.

Multifilter phase imaging with partially coherent light (MFPI-PC) is a promising new quantitative phase imaging method. However, the existing MFPI-PC method is based on the paraxial approximation. In the present work, an analytical nonparaxial partially coherent phase optical transfer function is derived. This enables the MFPI-PC to be extended to the realistic nonparaxial case. Simulations over a wide range of test phase objects as well as experimental measurements on a microlens array verify higher levels of imaging accuracy compared to the paraxial method. Unlike the paraxial version, the nonparaxial MFPI-PC with obliquity factor correction exhibits no systematic error. In addition, due to its analytical expression, the increase in computation time compared to the paraxial version is negligible.

The mediating effect of self-efficacy in the relationship between social support and post-traumatic stress disorder symptoms among patients with central system tumors in China: a cross-sectional study.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a disorder that can affect people following the experience of a traumatic event. Few studies have researched on PTSD symptoms of patients with central nervous system tumors. In this study, we aim to examine the association between social support and PTSD symptoms and to explore the mediating effect of self-efficacy in this relationship among patients with central nervous system tumors in China. METHODS: Questionnaires consisting of the Post-traumatic Stress Checklist-Civilian Version, the Duke-UNC Functional Social Support Questionnaire, the General Self-Efficacy Scale, as well as demographic and clinical factors were used to collect information of patients with central nervous system tumors in Liaoning Province, China. A total of 222 patients (effective response rate of 66.1%) became our subjects. Hierarchical linear regression analyses were performed to explore the association between social support and PTSD symptoms and the mediating effect of self-efficacy. RESULTS: After adjusting for demographic characteristics and tumor type, social support was negatively associated with the total score of PTSD symptoms (ß = -0.342, P < 0.01). Social support explained 8.8% of the variance in PTSD symptoms. Self-efficacy was found to partially mediate the relationship between social support and PTSD symptoms. CONCLUSIONS: Self-efficacy partially mediated the relationship between social support and PTSD symptoms. Interventions focusing on both social support and self-efficacy might be more useful than interventions only targeting either of them.

Which is the best treatment for melanoma brain metastases? A Bayesian network meta-analysis and systematic review.

OBJECTIVE: Melanoma has a high degree of central nervous system tropism, and there are many treatment modalities for melanoma brain metastases (MBM). The efficacy and toxicity of various treatments are still controversial. Therefore, they were evaluated by direct and indirect comparison to assist clinical decision-making in this study. METHOD: A total of 7 therapeutic modalities for MBM were studied. Retrieval was conducted through Embase, PubMed, Cochrane Library and Web of science databases and the quality of the included literature was evaluated. Meta-analysis and Bayesian network meta-analysis were performed using Review Manager and R language. RESULTS: A total of 10 articles were included with 836 MBM patients. Direct comparison showed that stereotactic radiotherapy combined with immunotherapy (SRS + IT) was superior to IT (HR = 0.66, 95%CI = 0.52-0.84) or SRS (HR = 0.81, 95%CI = 0.63-1.03) alone in improving intracranial progression-free survival (PFS). In terms of overall survival (OS), SRS + IT was superior to SRS alone (HR = 0.64, 95%CI = 0.49-0.83), or IT (HR = 0.59, 95%CI = 0.29-1.21). Rank probability and surface under the cumulative ranking curve (SUCRA) by indirect comparison showed that SRS + IT had the best effect on improving intracranial PFS (0.88) and OS (0.98). Additionally, various combination therapies, especially SRS + IT (0.72), increased the incidence of radiation necrosis (RN). In direct comparisons, SRS + IT (RR = 0.93, 95%CI = 0.47-1.83) and SRS + TT (targeted therapy) (RR = 0.24, 95%CI = 0.10-0.56) did not increase intracranial hemorrhage (ICH) compared with SRS. CONCLUSIONS: SRS + IT treatment was the best choice for MBM patients in both intracranial PFS and OS, even though it also led to an increased probability of RN.

The recent two decades of traumatic brain injury: a bibliometric analysis and systematic review.

BACKGROUND: Traumatic brain injury (TBI) is a serious public health burden worldwide, with a mortality rate of 20-30%; however, reducing the incidence and mortality rates of TBI remains a major challenge. This study provides a multidimensional analysis to explore the potential breakthroughs in TBI over the past two decades. MATERIALS AND METHODS: The authors used bibliometric and Latent Dirichlet Allocation (LDA) analyses to analyze publications focusing on TBI published between 2003 and 2022 from the Web of Science Core Collection (WOSCC) database to identify core journals and collaborations among countries/regions, institutions, authors, and research trends. RESULTS: Over the past 20 years, 41 545 articles on TBI from 3043 journals were included, with 12 916 authors from 20 449 institutions across 145 countries/regions. The annual number of publications has increased 10-fold compared to previous publications. This study revealed that high-income countries, especially the United States, have a significant influence. Collaboration was limited to several countries/regions. The LDA results indicated that the hotspots included four main areas: 'Clinical finding', 'Molecular mechanism', 'Epidemiology', and 'Prognosis'. Epidemiological research has consistently increased in recent years. Through epidemiological topic analysis, the main etiology of TBI has shifted from traffic accidents to falls in a demographically aging society. CONCLUSION: Over the past two decades, TBI research has developed rapidly, and its epidemiology has received increasing attention. Reducing the incidence of TBI from a preventive perspective is emerging as a trend to alleviate the future social burden; therefore, epidemiological research might bring breakthroughs in TBI.