Genome-Wide Mendelian Randomization Study Reveals Druggable Genes for Cerebral Small Vessel Disease.

BACKGROUND: Cerebral small vessel disease (CSVD) is a group of neurological disorders that affect the small blood vessels within the brain, for which no effective treatments are currently available. We conducted a Mendelian randomization (MR) study to identify candidate therapeutic genes for CSVD. METHODS: We retrieved genome-wide association study data from 6 recently conducted, extensive investigations focusing on CSVD magnetic resonance imaging markers and performed a 2-sample MR analysis to assess the potential causal effects of gene expression and protein level within druggable genes on CSVD in blood and brain tissues. Colocalization analyses and repeat studies were undertaken to verify the relationship. Additionally, mediation analysis was conducted to explore the potential mechanisms involving druggable genes and known risk factors for CSVD. Finally, phenome-wide MR analyses were applied to evaluate the potential adverse effects related to the identified druggable genes for CSVD treatment. RESULTS: Overall, 5 druggable genes consistently showed associations with CSVD in MR analyses across both the discovery and validation cohorts. Notably, the ALDH2 and KLHL24 genes were identified as associated with CSVD in both blood and brain tissues, whereas the genes ADRB1, BTN3A2, and EFEMP1 were exclusively detected in brain tissue. Moreover, mediation analysis elucidated the proportion of the total effects mediated by CSVD risk factors through candidate druggable genes, which ranged from 5.5% to 18.5%, and offered potential explanations for the observed results. A comprehensive phenome-wide MR analysis further emphasized both the therapeutic benefits and potential side effects of targeting these candidate druggable genes. CONCLUSIONS: This study provides genetic evidence supporting the potential therapeutic benefits of targeting druggable genes for treating CSVD, which will be useful for prioritizing CSVD drug development.

Single-Molecule Protein Analysis by Centrifugal Droplet Immuno-PCR with Magnetic Nanoparticles.

Detecting proteins in ultralow concentrations in complex media is important for many applications but often relies on complicated techniques. Herein, a single-molecule protein analyzer with the potential for high-throughput applications is reported. Gold-coated magnetic nanoparticles with DNA-labeled antibodies were used for target recognition and separation. The immunocomplex was loaded into microdroplets generated with centrifugation. Immuno-PCR amplification of the DNA enabled the quantification of proteins at the level of single molecules. As an example, ultrasensitive detection of α-synuclein, a biomarker for neurodegenerative diseases, is achieved. The limit of detection was determined to be ∼50 aM in buffer and ∼170 aM in serum. The method exhibited high specificity and could be used to analyze post-translational modifications such as protein phosphorylation. This study will inspire wider studies on single-molecule protein detection, especially in disease diagnostics, biomarker discovery, and drug development.

Automated diffusion-weighted image analysis along the perivascular space index reveals glymphatic dysfunction in association with brain parenchymal lesions.

Brain glymphatic dysfunction is critical in neurodegenerative processes. While animal studies have provided substantial insights, understandings in humans remains limited. Recent attention has focused on the non-invasive evaluation of brain glymphatic function. However, its association with brain parenchymal lesions in large-scale population remains under-investigated. In this cross-sectional analysis of 1030 participants (57.14 ± 9.34 years, 37.18% males) from the Shunyi cohort, we developed an automated pipeline to calculate diffusion-weighted image analysis along the perivascular space (ALPS), with a lower ALPS value indicating worse glymphatic function. The automated ALPS showed high consistency with the manual calculation of this index (ICC = 0.81, 95% CI: 0.662-0.898). We found that those with older age and male sex had lower automated ALPS values (ß = -0.051, SE = 0.004, p < .001, per 10 years, and ß = -0.036, SE = 0.008, p < .001, respectively). White matter hyperintensity (ß = -2.458, SE = 0.175, p < .001) and presence of lacunes (OR = 0.004, 95% CI < 0.002-0.016, p < .001) were significantly correlated with decreased ALPS. The brain parenchymal and hippocampal fractions were significantly associated with decreased ALPS (ß = 0.067, SE = 0.007, p < .001 and ß = 0.040, SE = 0.014, p = .006, respectively) independent of white matter hyperintensity. Our research implies that the automated ALPS index is potentially a valuable imaging marker for the glymphatic system, deepening our understanding of glymphatic dysfunction.

Lateral shearing interferometry method based on double-checkerboard grating by suppressing aliasing effect.

Ronchi lateral shearing interferometry is a promising wavefront sensing technology with the advantages of simple structure and no reference light, which can realize a high-precision wavefront aberration measurement. To obtain shear information in both directions, the conventional double-Ronchi interferometer sequentially applies two orthogonal one-dimensional Ronchi gratings as the object-plane splitting element of the optics under test. Simultaneously, another Ronchi grating is positioned on the image plane in the same orientation to capture two sets of interferograms, thereby enabling two-dimensional wavefront reconstruction. Mechanical errors will inevitably be introduced during grating conversion, affecting reconstruction accuracy. Based on this, we propose a lateral shearing interferometry applying double-checkerboard grating. Only unidirectional phase shift is needed to obtain shear information in two directions while evading the grating conversion step, aiming to streamline operational processes and mitigate the potential for avoidable errors. We employ scalar diffraction theory to analyze the full optical path propagation process of the double-checkerboard shearing interferometry and introduce a new reconstruction algorithm to effectively extract the two-dimensional shear phase by changing the grating morphology, suppressing the aliasing effect of irrelevant diffraction orders. We reduce the fitting error through iterative optimization to realize high-precision wavefront reconstruction. Compared with conventional Ronchi lateral shearing interferometry, the proposed method exhibits better robustness and stability in noisy environments.

UV-enhanced photorefractive response rate in a thin-film lithium niobate microdisk.

The photorefractive (PR) effect plays a critical role in emerging photonic technologies, including dynamic volume holography and on-chip all-optical functionalities. Nevertheless, its slow response rate has posed a significant obstacle to its practical application. Here, we experimentally demonstrate the enhancement of the PR response rate in a high-Q thin-film lithium niobate (TFLN) microdisk under UV light irradiation. At an irradiation intensity of 30 mW/cm2, the PR effect achieves a high response bandwidth of approximately 256 kHz. By employing this UV-assisted PR effect, we have achieved rapid laser-cavity locking and self-stabilization, where perturbations are automatically compensated. This technique paves the way toward real-time dynamic holography, editable photonic devices on a lithium niobate platform, and high-speed all-optical information processing.

Enhanced Frequency Conversion in Parity-Time Symmetry Line.

Non-Hermitian degeneracies reveal intriguing and nontrivial behaviors in open physical systems. Examples like parity-time (PT) symmetry breaking, topological encircling chirality, and enhanced sensing near an exceptional point (EP) are often associated with the abrupt nature of the phase transition around these degeneracies. Here we experimentally observe a cavity-enhanced second-harmonic frequency (SHG) conversion on a PT symmetry line, i.e., a set consisting of open-ended isofrequency or isoloss lines, both terminated at EPs on the Riemann surface in parameter space. The enhancement factor can reach as high as 300, depending on the crossing point whether in the symmetry or the broken phase of the PT line. Moreover, such enhancement of SHG enables sensitive distance sensing with a nanometer resolution. Our works may pave the way for practical applications in sensing, frequency conversion, and coherent wave control.

The genetic risk factors for cerebral venous thrombosis: a case-control study in a Chinese national comprehensive hospital.

BACKGROUND: About 13-25% of cerebral venous thrombosis (CVT) cases lack clear etiology, which may be associated with underlying genetic factors. This study aims to investigate genetic factors in CVT patients using whole exome sequencing (WES). METHODS: Thirty-eight CVT patients hospitalized underwent WES. 977 subjects with WES data from a community cohort study --the Shunyi cohort were as the control group. Using bioinformatics analysis, differential genes with rare damaging variants between two groups were filtered (P < 0.05). KEGG enrichment analysis was performed on the screened genes to identify pathways associated with CVT. RESULTS: Through analysis of medical history, routine tests, and imaging examinations, the etiology of 38 patients: 8 cases of antiphospholipid syndrome, 6 cases with hematologic diseases, 3 cases of protein C deficiency, and 2 cases of protein S deficiency. Five cases occurred during pregnancy or puerperium, and 3 cases had a history of oral contraceptive use, and so on. The etiology was unknown in 12 cases (31.6%), and the etiology of 4 patients were further clarified through WES: F9 c.838 + 1_838 + 16del, Hemizygote: F9 EX1-EX7 Dup; CBS c.430G > A, CBS c.949 A > G; F2 c.1787G > A; SERPINC1 c.409-11G > T. Comparing the WES data of two groups, a total of 179 different genes with rare damaging variants were screened (P < 0.05), with 5 genes of interest (JAK2, C3, PROC, PROZ, SERPIND1). Enrichment analysis of the 179 different genes revealed the complement and coagulation pathway and the mitogen activated protein kinases (MAPK) pathway were associated with CVT. CONCLUSION: For CVT patients with unknown etiology, WES could help identify the cause of CVT early, which is of great significance for treatment decisions and prognosis. In addition to the complement and coagulation pathway, MAPK pathway is associated with CVT, potentially related to platelet regulation and inflammatory response.

Current status and value of testing antiphospholipid antibody in patients with acute ischemic stroke: a retrospective single-center study in China.

BACKGROUND AND PURPOSE: Testing for antiphospholipid antibodies (aPL) is useful to determine the cause of ischemic stroke in young and female patients. However, the clinical relevance of aPL in older patients with ischemic stroke remains unclear. We aimed to explore the status and diagnostic value of initial aPL testing in all patients with acute ischemic stroke. METHODS: We retrospectively analyzed patients with acute ischemic stroke who were consecutively hospitalized in our hospital between June 2012 and January 2022 and investigated the factors associated with performing aPL screening in real-world clinical practice. Furthermore, factors associated with initial aPL positivity were evaluated by comparing the demographic, etiological, and therapeutic characteristics. RESULTS: Of 1209 patients, 287 (23.7%) were tested for aPL and 58 (20.2%) tested positive. Physicians tended to conduct aPL testing on female patients (P<0.001), younger patients (P<0.001), patients with fewer vascular risk factors (P<0.001), and multiple infarctions in the multivascular blood supply area (P<0.001). Multivariate logistic regression analysis showed that only stroke of other determined etiology type was a significant influencing factor for positive aPL results (OR 2.97, 95% CI 1.137, 7.774, P=0.026), adjusting for sex, age, and causes of stroke, etc. CONCLUSION: Approximately one-quarter of the patients with acute ischemic stroke were tested for aPL. Age, sex, number of vascular risk factors, and neuroimaging features affected the discretion in performing aPL testing. aPL testing may be appropriate in older patients with no identified cause of ischemic stroke and may provide additional diagnostic opportunities for acute ischemic stroke.

Rifampicin synergizes the toxicity of insecticides against the green peach aphid, Myzus persicae.

Myzus persicae is an important pest that has developed resistance to nearly all currently used insecticidal products. The employment of insecticide synergists is one of the effective strategies that need to be developed for the management of this resistance. Our study showed that treatment with a combination of the antibiotic, rifampicin, with imidacloprid, cyantraniliprole, or clothianidin significantly increased their toxicities against M. persicae, by 2.72, 3.59, and 2.41 folds, respectively. Rifampicin treatment led to a noteworthy reduction in the activities of multifunctional oxidases (by 32.64%) and esterases (by 23.80%), along with a decrease in the expression of the CYP6CY3 gene (by 58.57%) in M. persicae. It also negatively impacted the fitness of the aphids, including weight, life span, number of offspring, and elongation of developmental duration. In addition, bioassays showed that the combination of rifampicin and a detoxification enzyme inhibitor, piperonyl butoxide, or dsRNA of CYP6CY3 further significantly improved the toxicity of imidacloprid against M. persicae, by 6.19- and 7.55-fold, respectively. The present study suggests that development of active ingredients such as rifampicin as candidate synergists, show promise to overcome metabolic resistance to insecticides in aphids.

Automatic Detection of Thyroid Nodule Characteristics From 2D Ultrasound Images.

Thyroid cancer is one of the common types of cancer worldwide, and Ultrasound (US) imaging is a modality normally used for thyroid cancer diagnostics. The American College of Radiology Thyroid Imaging Reporting and Data System (ACR TIRADS) has been widely adopted to identify and classify US image characteristics for thyroid nodules. This paper presents novel methods for detecting the characteristic descriptors derived from TIRADS. Our methods return descriptions of the nodule margin irregularity, margin smoothness, calcification as well as shape and echogenicity using conventional computer vision and deep learning techniques. We evaluate our methods using datasets of 471 US images of thyroid nodules acquired from US machines of different makes and labeled by multiple radiologists. The proposed methods achieved overall accuracies of 88.00%, 93.18%, and 89.13% in classifying nodule calcification, margin irregularity, and margin smoothness respectively. Further tests with limited data also show a promising overall accuracy of 90.60% for echogenicity and 100.00% for nodule shape. This study provides an automated annotation of thyroid nodule characteristics from 2D ultrasound images. The experimental results showed promising performance of our methods for thyroid nodule analysis. The automatic detection of correct characteristics not only offers supporting evidence for diagnosis, but also generates patient reports rapidly, thereby decreasing the workload of radiologists and enhancing productivity.

Correlation between Circle of Willis Configuration and Intracranial Arterial Dolichoectasia, and Genetic Contributions.

OBJECTIVES: Intracranial arterial dolichoectasia (IADE) is characterized by the dilation, elongation, and tortuosity of intracranial arteries. We aimed to investigate the association between variations of the Circle of Willis (COW) and IADE in the general population, as well as estimate the genetic correlation between COW variations and IADE. METHODS: A total of 981 individuals from a population-based cohort were included. Brain magnetic resonance angiography was performed to assess COW variants and measure the diameters of intracranial arteries. IADE was defined as a total intracranial volume-adjusted diameter ≥ 2 standard deviations. Logistic regression models were used to analyze the association between COW variations and IADE. The heritability and genetic correlation were estimated using genome-wide complex trait analysis (GCTA) based on single nucleotide polymorphism (SNP) array data. RESULTS: The prevalence of IADE was 6.2%. Hypoplastic/absent A1 segments were associated with an increase in contralateral ICA diameter (ß ± SE, 0.279 ± 0.049; p = 0.001) and a decrease in ipsilateral ICA diameter (ß ± SE, -0.300 ± 0.050; p = 0.001). Fetal-type posterior cerebral artery (FTP) was associated with a larger ICA diameter (ß ± SE, 0.326 ± 0.048; p = 0.001) and a smaller BA diameter (ß ± SE, -0.662 ± 0.043; p = 0.001). FTP revealed a positive genetic correlation with ICA dilation (rG = 0.259 ± 0.175; p = 0.0009) and a negative genetic correlation with BA dilation (rG = -0.192 ± 0.153, p = 0.015). CONCLUSIONS: There was an association between COW variations and larger intracranial arterial diameters in the general population. Genetic factors may play a role in the development of intracranial arterial dilation and the formation of COW variants.

Pembrolizumab for the treatment of progressive multifocal leukoencephalopathy in China.

The aim of this study is to analyze the clinical characteristics and outcomes of Chinese patients with progressive multifocal leukoencephalopathy (PML) who were treated with programmed cell death protein 1 (PD1) blockade therapies. We retrospectively analyzed patients who were admitted to our hospital between October 1, 2020, and October 1, 2022, diagnosed with PML and treated with PD1 blockade therapies. Four patients with PML who were treated with PD1 blockade therapies were identified. All patients were male, and their ages ranged from 19 to 54 years old. One patient (Case 2) exhibited mild pleocytosis, while three patients (Cases 2-4) had markedly reduced T lymphocyte cell counts prior to treatment. The time interval between symptom onset and treatment initiation ranged from six to 54 weeks. All patients received pembrolizumab treatment, with a total of two to four doses administered. Three patients who responded to pembrolizumab treatment showed clinical improvement starting around 8 weeks after the initiation of therapy. Although one patient did not show clinical improvement, they ultimately survived until the last follow-up. None of the patients in this study exhibited immune-related adverse events or immune reconstitution inflammatory syndrome. PD1 blockade appears to be a promising novel therapeutic option for PML; additional prospective studies are necessary to confirm its efficacy.

Solving digital image correlation with neural networks constrained by strain-displacement relations.

The use of supervised neural networks is a new approach to solving digital image correlation (DIC) problems, but the existing methods solely adopt the black-box neural network, i.e., the mapping from speckle image pair (reference image and deformed image) to multiple deformation fields (displacement fields and strain fields) is directly established without considering the physical constraints between the fields, causing a low level of accuracy that is even inferior to that of Subset-DIC. In this work, we proposed a deep learning model by introducing strain-displacement relations into a neural network, in which the effect of errors both in displacement and strain are considered in the network training. The back-propagation process of the proposed model is derived, and the solution scheme is implemented by Python. The performance of the proposed model is evaluated by simulation and real DIC experiments, and the results show that adding physical constraints to the neural network can significantly improve prediction accuracy.

The Serotonergic System and Amyotrophic Lateral Sclerosis: A Review of Current Evidence.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the premature death of motor neurons. Serotonin (5-HT) is a crucial neurotransmitter, and its dysfunction, whether as a contributor or by-product, has been implicated in ALS pathogenesis. Here, we summarize current evidence linking serotonergic alterations to ALS, including results from post-mortem and neuroimaging studies, biofluid testing, and studies of ALS animal models. We also discuss the possible role of 5-HT in modulating some important mechanisms of ALS (i.e. glutamate excitotoxity and neuroinflammation) and in regulating ALS phenotypes (i.e. breathing dysfunction and metabolic defects). Finally, we discuss the promise and limitations of the serotonergic system as a target for the development of ALS biomarkers and therapeutic approaches. However, due to a relative paucity of data and standardized methodologies in previous studies, proper interpretation of existing results remains a challenge. Future research is needed to unravel the mechanisms linking serotonergic pathways and ALS and to provide valid, reproducible, and translatable findings.

Autoimmune Cerebellar Ataxia: Etiology and Clinical Characteristics of a Case Series from China.

Autoimmune cerebellar ataxia (ACA) is an important and potentially treatable cause of sporadic cerebellar syndrome, but studies with large sample size are limited. This study reported a large ACA series in China and described its etiology and clinical characteristics. We reviewed all ACA patients from our hospital (2013-2021) and analyzed their clinical and paraclinical features, treatment, and outcome. ACA subtypes investigated included paraneoplastic cerebellar degeneration (PCD), primary autoimmune cerebellar ataxia (PACA), anti-glutamate decarboxylase (GAD)-associated cerebellar ataxia, opsoclonus-myoclonus syndrome (OMS), Miller Fisher syndrome (MFS), and ACA-associated with autoimmune encephalitis. A total of 127 patients were identified and 40.9% were male. The median onset age was 47.0 years. Gait ataxia was the most prevalent feature followed by limb ataxia, dizziness, and dysarthria/dysphagia. Extracerebellar manifestations included pyramidal signs (28.3%) and peripheral neuropathy/radiculopathy (15.0%). ACA subtypes were PCD (30.7%), PACA (37.8%), ACA associated with autoimmune encephalitis (12.6%), anti-GAD-associated ACA (8.7%), MFS (7.1%), and OMS (3.1%). Neuronal antibodies were positive in 67.7% of patients. Brain magnetic resonance imaging was unremarkable (55.7%) or showed atrophy (18.3%) or abnormal signal intensity (26.1%, most of which was extracerebellar). Although most patients received immunotherapy, the modified Rankin scale at last follow-up was ≤ 2 in only 47.3% patients. Thirteen patients died and 24 relapsed. Compared with PACA, PCD patients were older and had poorer outcome. This study illustrates the heterogeneity in the clinical features of ACA and suggests the importance of neuronal antibody testing in ACA diagnosis. PCD and PACA are the dominant ACA subtypes, and the former has a less favorable prognosis.

The prevalence and prognosis of asymptomatic intracranial atherosclerosis in a community-based population: Results based on high-resolution magnetic resonance imaging.

BACKGROUND AND PURPOSE: Intracranial atherosclerotic disease (ICAD) is a major cause of ischemic stroke in China, but the prevalence and prognosis of asymptomatic ICAD detected using high-resolution magnetic resonance imaging (HR-MRI) is largely unknown. The aim of this study was to investigate the prevalence and prognosis in order to guide neurologists in interpreting ICAD detected on HR-MRI. METHODS: We included stroke-free participants from a community-based prospective cohort (Shunyi study participants) who underwent HR-MRI between July 2014 and April 2016. The participants were divided into two groups: those with or without ICAD (ICAD+ and ICAD- , respectively). ICAD included intracranial artery stenosis and non-stenotic plaque. The primary outcome was ischemic stroke. Cox proportional hazard models were used to evaluate the association between ICAD and event outcomes. RESULTS: A total of 1060 stroke-free participants evaluated by HR-MRI were included from the Shunyi study. The median age at HR-MRI was 56 years and 64.7% were female. The ICAD prevalence was 36.3% (n = 385). The ICAD+ group was older and had more cerebrovascular risk factors. The rates of ischemic stroke in the ICAD- and ICAD+ groups were 1.3% (n = 9) and 5.2% (n = 20), respectively, with a median follow-up time of 54 months. ICAD was associated with an increased risk of ischemic stroke in the unadjusted and adjusted Cox models, with hazard ratios of 4.12 (95% confidence interval [CI] 1.87-9.05) and 2.50 (95% CI 1.05-5.94), respectively. The greatest risk of an event outcome was observed in participants with ≥70% stenosis or occlusion. The features of high-risk plaques were also identified. CONCLUSIONS: We found that ICAD detected using HR-MRI increases the long-term risk of a first-ever ischemic stroke in a stroke-free population, suggesting that the current primary prevention protocol of stroke awaits further optimization.

Association between Anatomical Variations of the Circle of Willis and Covert Vascular Brain Injury in the General Population.

BACKGROUND AND PURPOSE: The circle of Willis (COW) is a circulatory anastomosis located at the base of the brain. Little is known about the association between covert vascular brain injury and COW configurations in the general population. We explored this relationship in a community-based Chinese sample. METHODS: A total of 1,055 patients (mean age, 54.8 ± 8.9 years; 36.0% men) without intracranial arterial stenosis were included in the analysis. Magnetic resonance imaging was performed to evaluate the presence of imaging markers of covert vascular brain injury, including white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs), enlarged perivascular spaces, and brain atrophy. Magnetic resonance angiography was used to classify the COW configurations according to the completeness, symmetry, and presence of the fetal posterior cerebral artery (FTP). The association between vascular lesions and variations in COW was analyzed. RESULTS: Among the 1,055 patients, 104 (9.9%) had a complete COW. Completeness correlated with age (p = 0.001). Incomplete COW was positively associated with WMH severity (OR = 2.071; 95% CI, 1.004-4.270) and CMB presence (OR = 1.542; 95% CI, 1.012-2.348), independent of age and sex. The presence of FTP was associated with lacunes (OR = 1.878; 95% CI, 1.069-3.298), more severe WMHs (OR = 1.739; 95% CI, 1.064-2.842), and less severe enlarged perivascular spaces (OR = 0.562; 95% CI, 0.346-0.915). CONCLUSIONS: COW configuration was significantly related to various covert vascular brain injuries.

Gene-mapping study of extremes of cerebral small vessel disease reveals TRIM47 as a strong candidate.

Cerebral small vessel disease is a leading cause of stroke and a major contributor to cognitive decline and dementia, but our understanding of specific genes underlying the cause of sporadic cerebral small vessel disease is limited. We report a genome-wide association study and a whole-exome association study on a composite extreme phenotype of cerebral small vessel disease derived from its most common MRI features: white matter hyperintensities and lacunes. Seventeen population-based cohorts of older persons with MRI measurements and genome-wide genotyping (n = 41 326), whole-exome sequencing (n = 15 965), or exome chip (n = 5249) data contributed 13 776 and 7079 extreme small vessel disease samples for the genome-wide association study and whole-exome association study, respectively. The genome-wide association study identified significant association of common variants in 11 loci with extreme small vessel disease, of which the chr12q24.11 locus was not previously reported to be associated with any MRI marker of cerebral small vessel disease. The whole-exome association study identified significant associations of extreme small vessel disease with common variants in the 5' UTR region of EFEMP1 (chr2p16.1) and one probably damaging common missense variant in TRIM47 (chr17q25.1). Mendelian randomization supports the causal association of extensive small vessel disease severity with increased risk of stroke and Alzheimer's disease. Combined evidence from summary-based Mendelian randomization studies and profiling of human loss-of-function allele carriers showed an inverse relation between TRIM47 expression in the brain and blood vessels and extensive small vessel disease severity. We observed significant enrichment of Trim47 in isolated brain vessel preparations compared to total brain fraction in mice, in line with the literature showing Trim47 enrichment in brain endothelial cells at single cell level. Functional evaluation of TRIM47 by small interfering RNAs-mediated knockdown in human brain endothelial cells showed increased endothelial permeability, an important hallmark of cerebral small vessel disease pathology. Overall, our comprehensive gene-mapping study and preliminary functional evaluation suggests a putative role of TRIM47 in the pathophysiology of cerebral small vessel disease, making it an important candidate for extensive in vivo explorations and future translational work.

Topic and Trend Analysis of Weibo Discussions About COVID-19 Medications Before and After China's Exit from the Zero-COVID Policy: Retrospective Infoveillance Study.

BACKGROUND: After 3 years of its zero-COVID policy, China lifted its stringent pandemic control measures with the announcement of the 10 new measures on December 7, 2022. Existing estimates suggest 90%-97% of the total population was infected during December. This change created a massive demand for COVID-19 medications and treatments, either modern medicines or traditional Chinese medicine (TCM). OBJECTIVE: This study aimed to explore (1) how China's exit from the zero-COVID policy impacted media and the public's attention to COVID-19 medications; (2) how social COVID-19 medication discussions were related to existing model estimates of daily cases during that period; (3) what the diversified themes and topics were and how they changed and developed from November 1 to December 31, 2022; and (4) which topics about COVID-19 medications were focused on by mainstream and self-media accounts during the exit. The answers to these questions could help us better understand the consequences of exit strategies and explore the utilities of Sina Weibo data for future infoveillance studies. METHODS: Using a scrapper for data retrieval and the structural topic modeling (STM) algorithm for analysis, this study built 3 topic models (all data, before a policy change, and after a policy change) of relevant discussions on the Chinese social media platform Weibo. We compared topic distributions against existing estimates of daily cases and between models before and after the change. We also compared proportions of weibos published by mainstream versus self-media accounts over time on different topics. RESULTS: We found that Weibo discussions shifted sharply from concerns of social risks (case tracking, governmental regulations, etc) to those of personal risks (symptoms, purchases, etc) surrounding COVID-19 infection after the exit from the zero-COVID policy. Weibo topics of "symptom sharing" and "purchase and shortage" of modern medicines correlated more strongly with existing susceptible-exposed-infected-recovered (SEIR) model estimates compared to "TCM formulae" and other topics. During the exit, mainstream accounts showed efforts to specifically engage in topics related to worldwide pandemic control policy comparison and regulations about import and reimbursement of medications. CONCLUSIONS: The exit from the zero-COVID policy in China was accompanied by a sudden increase in social media discussions about COVID-19 medications, the demand for which substantially increased after the exit. A large proportion of Weibo discussions were emotional and expressed increased risk concerns over medication shortage, unavailability, and delay in delivery. Topic keywords showed that self-medication was sometimes practiced alone or with unprofessional help from others, while mainstream accounts also tried to provide certain medication instructions. Of the 16 topics identified in all 3 STM models, only "symptom sharing" and "purchase and shortage" showed a considerable correlation with SEIR model estimates of daily cases. Future studies could consider topic exploration before conducting predictive infoveillance analysis, even with narrowly defined search criteria with Weibo data.

Real-time carotid plaque recognition from dynamic ultrasound videos based on artificial neural network.

PURPOSE: Carotid ultrasound allows noninvasive assessment of vascular anatomy and function with real-time display. Based on the transfer learning method, a series of research results have been obtained on the optimal image recognition and analysis of static images. However, for carotid plaque recognition, there are high requirements for self-developed algorithms in real-time ultrasound detection. This study aims to establish an automatic recognition system, Be Easy to Use (BETU), for the real-time and synchronous diagnosis of carotid plaque from ultrasound videos based on an artificial neural network. MATERIALS AND METHODS: 445 participants (mean age, 54.6±7.8 years; 227 men) were evaluated. Radiologists labeled a total of 3259 segmented ultrasound images from 445 videos with the diagnosis of carotid plaque, 2725 images were collected as a training dataset, and 554 images as a testing dataset. The automatic plaque recognition system BETU was established based on an artificial neural network, and remote application on a 5G environment was performed to test its diagnostic performance. RESULTS: The diagnostic accuracy of BETU (98.5%) was consistent with the radiologist's (Kappa = 0.967, P < 0.001). Remote diagnostic feedback based on BETU-processed ultrasound videos could be obtained in 150ms across a distance of 1023 km between the ultrasound/BETU station and the consultation workstation. CONCLUSION: Based on the good performance of BETU in real-time plaque recognition from ultrasound videos, 5G plus Artificial intelligence (AI)-assisted ultrasound real-time carotid plaque screening was achieved, and the diagnosis was made.