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AIMS: Circulating levels of sphingosine 1-phosphate (S1P), an HDL-associated ligand for endothelial cell (EC) protective S1P receptor-1 (S1PR1), are reduced in disease states associated with endothelial dysfunction. Yet as S1PR1 has high affinity for S1P and can be activated by ligand-independent mechanisms and EC-autonomous S1P production, it is unclear if relative reductions in circulating S1P impact endothelial function. It is also unclear how EC S1PR1 insufficiency, whether induced by ligand deficiency or by S1PR1-directed immunosuppressive therapy, affects different vascular subsets. METHODS AND RESULTS: We here fine-map the zonation of S1PR1 signalling in the murine blood and lymphatic vasculature, superimpose cell type-specific and relative deficiencies in S1P production to define ligand source- and dose-dependence, and correlate receptor engagement to essential functions. In naïve blood vessels, despite broad expression, EC S1PR1 engagement was restricted to resistance-size arteries, lung capillaries and high-endothelial venules (HEV). Similar zonation was observed for albumin extravasation in EC S1PR1 deficient mice, and brain extravasation was reproduced with arterial EC-selective S1pr1 deletion. In lymphatic EC, S1PR1 engagement was high in collecting vessels and lymph nodes and low in terminal capillaries that drain tissue fluids. While EC S1P production sustained S1PR1 signaling in lymphatics and HEV, hematopoietic cells provided â¼90% of plasma S1P and sustained signaling in resistance arteries and lung capillaries. S1PR1 signaling and endothelial function were both surprisingly sensitive to reductions in plasma S1P with apparent saturation around 50% of normal levels. S1PR1 engagement did not depend on sex or age, but modestly increased in arteries in hypertension and diabetes. Sphingosine kinase (Sphk)-2 deficiency also increased S1PR1 engagement selectively in arteries, which could be attributed to Sphk1-dependent S1P release from perivascular macrophages. CONCLUSIONS: This study highlights vessel subtype-specific S1PR1 functions and mechanisms of engagement and supports the relevance of S1P as circulating biomarker for endothelial function.
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Self-assembled fluorescent particles have shown promise as a potential structure for random lasers. However, obtaining micron-sized random lasers made with fluorescent particles remains a challenge. Theoretically, achieving micron-sized random lasers could be possible by assembling supraparticles composed of colloidal particles. Despite extensive research on supraparticles, the generation of random lasers from this structure is rarely reported. In this study, we introduce a rapid and efficient method for producing supraparticles from fluorescent particles. The resulting supraparticles exhibit diameters ranging from 50 to 150â µm with particles well-connected and uniformly distributed throughout their structure. Under optical excitation, supraparticles with a diameter larger than 80â µm demonstrate lasing emission with a threshold of approximately 77â µJ·mm-2. Larger supraparticles exhibit a distinct redshift in lasing wavelength compared to the smaller ones. Specifically, the central peak lasing wavelength shows a shift of about 7.5â nm as the supraparticle diameter increases from 80 to 150â µm.
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BACKGROUND: Juvenile Xanthogranuloma (JXG) is a non-Langerhans cell histiocytosis, occurring mainly in infancy. With an extracutaneous lesion, its diagnosis is difficult, because of a wide clinical spectrum. Here we demonstrate and characterize imaging features of 11 patients with JXG of the head and neck in various locations. MATERIAL AND METHODS: We recorded clinical data and reviewed all imaging studies of 11 patients with JXG of the head and neck. Ultrasonography (US) alone was performed in 1 patient; MRI alone in 6 patients; US and MRI in 1 patient; and US, CT, and MRI in 3 patients. We evaluated the following characteristics in all studies: location and number of lesions, echogenicity and vascularization on US, density on CT, signal intensity on T 1 - and T 2 -weighted images, ADC and enhancement on MRI, and tumor boundaries and bone involvement. RESULTS: Lesions were well-defined in 9 cases, and bone erosion was present in 2. On US, lesions were hypoechoic or hyperechoic and with or without vascularization. On CT, lesions were hyper-dense, with no calcification. On MRI, lesions were mildly hyper-intense or iso-intense on T 1 -weighted images in 8 of 9 patients, hypo-intense on T2-weighted images in 7 of 10, low ADC in 7 of 9, and enhancement in 7 of 7. CONCLUSIONS: The diagnosis of extra cutaneous JXG may be proposed, with the following suggestive criteria: age < 1 year, well-defined lesion, mild hyper-intensity on T 1 -weighted images, hypo-intensity on T 2 -weighted images, low ADC, enhancement, and possible adjacent bone involvement.
Subject(s)
Head , Magnetic Resonance Imaging , Ultrasonography , Xanthogranuloma, Juvenile , Humans , Xanthogranuloma, Juvenile/diagnostic imaging , Xanthogranuloma, Juvenile/pathology , Male , Female , Child, Preschool , Infant , Child , Magnetic Resonance Imaging/methods , Ultrasonography/methods , Head/diagnostic imaging , Head/pathology , Neck/diagnostic imaging , Neck/pathology , Tomography, X-Ray Computed , AdolescentABSTRACT
BACKGROUND: High-quality contraceptive counselling can accelerate global efforts to reduce the unmet need for and suboptimal use of modern contraceptives. This study aims to identify a package of interventions designed to strengthen in Pakistan and Nigeria and determine their effectiveness in increasing client-level decision-making, autonomy and meeting of contraceptive needs. METHODS: A multisite, two-stage and five-phase intervention design will start with a pre-formative, formative, design, experimental and reflective phase. The pre-formative phase will map potential study sites and establish the sampling frame. The two-part formative phase will first use participatory approaches to identify clients' perspectives, including young couples and providers, to ensure research contextualisation and address each interest group's needs and priorities followed by clinical observations of client-provider encounters to document routine care. The design workshop in the third phase will result in the development of a package of contraceptive counselling interventions. In the fourth experimental phase, a multi-intervention, three-arm, single-blinded, parallel cluster randomised-controlled trial will compare routine care (arm 1) with the contraceptive counselling package (arm 2) and the same package combined with wider methods availability (arm 3). The study aims to enrol a total of 7920 participants. The reflective phase aims to identify implementation barriers and enablers. The outcomes are clients' level of decision-making autonomy and use of modern contraceptives. ETHICS AND DISSEMINATION: Ethical approval for this study was obtained from the WHO Scientific and Ethics Review Committee (Protocol ID Pakistan: ERC 006232 and Nigeria ERC: 006523). Each study site is required and has obtained the necessary ethical and regulatory approvals that are required in each specific country. Findings will be presented at local, national and international conferences and disseminated by peer-review publications. TRIAL REGISTRATION NUMBER: NCT06081842.
Subject(s)
Contraception , Counseling , Family Planning Services , Humans , Pakistan , Nigeria , Counseling/methods , Family Planning Services/methods , Female , Contraception/methods , Male , Empowerment , Contraception Behavior , Adult , Decision Making , AdolescentABSTRACT
Google Classroom is a virtual education platform created by Google that allows both instructors and learners to actively participate in educational environments inside and outside of the classroom in an innovative way. This research aims to determine how university students perceived the adoption of Google Classroom in writing classes. This research was a convergent parallel mix-methods approach in which data were gathered through a 5-point Likert scale questionnaire and semi-structured interviews. The participants of this study included 130 university students in Vietnam. The results revealed that students expressed their approval of using Google Classroom in writing classes and that they had a positive view since it benefited them greatly in their learning writing process. This study suggests practical implications for language educators to use Google Classroom in writing classes.
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Combination of waning immunity and lower effectiveness against new SARS-CoV-2 variants of approved COVID-19 vaccines necessitates new vaccines. We evaluated two doses, 28 days apart, of ARCT-154, a self-amplifying mRNA COVID-19 vaccine, compared with saline placebo in an integrated phase 1/2/3a/3b controlled, observer-blind trial in Vietnamese adults (ClinicalTrial.gov identifier: NCT05012943). Primary safety and reactogenicity outcomes were unsolicited adverse events (AE) 28 days after each dose, solicited local and systemic AE 7 days after each dose, and serious AEs throughout the study. Primary immunogenicity outcome was the immune response as neutralizing antibodies 28 days after the second dose. Efficacy against COVID-19 was assessed as primary and secondary outcomes in phase 3b. ARCT-154 was well tolerated with generally mild-moderate transient AEs. Four weeks after the second dose 94.1% (95% CI: 92.1-95.8) of vaccinees seroconverted for neutralizing antibodies, with a geometric mean-fold rise from baseline of 14.5 (95% CI: 13.6-15.5). Of 640 cases of confirmed COVID-19 eligible for efficacy analysis most were due to the Delta (B.1.617.2) variant. Efficacy of ARCT-154 was 56.6% (95% CI: 48.7- 63.3) against any COVID-19, and 95.3% (80.5-98.9) against severe COVID-19. ARCT-154 vaccination is well tolerated, immunogenic and efficacious, particularly against severe COVID-19 disease.
Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Humans , COVID-19 Vaccines/immunology , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , COVID-19/immunology , Female , Male , SARS-CoV-2/immunology , SARS-CoV-2/genetics , Adult , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/immunology , Middle Aged , Immunogenicity, Vaccine , Young Adult , Vaccine Efficacy , Vietnam , Adolescent , mRNA Vaccines , Vaccines, Synthetic/immunology , Vaccines, Synthetic/adverse effects , Vaccines, Synthetic/administration & dosageABSTRACT
Chrysanthemum morifolium is a valuable plant that contains a wide range of phytochemical compounds and exhibits various biological activities. Ethanol extracts from both the leaves and flowers of 17 different cultivars of C. morifolium were tested for antioxidant activities using the 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) assays and were quantitatively analyzed for 12 phenolic compounds using high-performance liquid chromatography with diode-array detection. We found that the 'Ford' and 'Raina' cultivars demonstrated strong antioxidant abilities and high phenolic compound contents compared to other cultivars, while the flowers of 'Cielo' and the leaves of 'White Cap' exhibited low antioxidant capacity in both assays. The 'Cielo' cultivar also displayed the lowest compound contents. Additionally, in most samples, 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid stood out as high-content compounds in the extracts. This study provides foundational knowledge that can be used for selecting appropriate C. morifolium cultivars for further research. Moreover, the 'Ford' and 'Raina' cultivars, containing high amounts of bioactive compounds and showing superior antioxidant ability, could be applied to produce health-beneficial products.
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Accumulation of sphingolipids, especially sphingosines, in the lysosomes is a key driver of several lysosomal storage diseases. The transport mechanism for sphingolipids from the lysosome remains unclear. Here, we identified SPNS1, which shares the highest homology to SPNS2, a sphingosine-1-phosphate (S1P) transporter, functions as a transporter for lysolipids from the lysosome. We generated Spns1-KO cells and mice and employed lipidomic and metabolomic approaches to reveal SPNS1 ligand identity. Global KO of Spns1 caused embryonic lethality between E12.5 and E13.5 and an accumulation of sphingosine, lysophosphatidylcholines (LPC), and lysophosphatidylethanolamines (LPE) in the fetal livers. Similarly, metabolomic analysis of livers from postnatal Spns1-KO mice presented an accumulation of sphingosines and lysoglycerophospholipids including LPC and LPE. Subsequently, biochemical assays showed that SPNS1 is required for LPC and sphingosine release from lysosomes. The accumulation of these lysolipids in the lysosomes of Spns1-KO mice affected liver functions and altered the PI3K/AKT signaling pathway. Furthermore, we identified 3 human siblings with a homozygous variant in the SPNS1 gene. These patients suffer from developmental delay, neurological impairment, intellectual disability, and cerebellar hypoplasia. These results reveal a critical role of SPNS1 as a promiscuous lysolipid transporter in the lysosomes and link its physiological functions with lysosomal storage diseases.
Subject(s)
Disease Models, Animal , Lysosomal Storage Diseases , Lysosomes , Mice, Knockout , Animals , Female , Humans , Male , Mice , Liver/metabolism , Lysophospholipids/metabolism , Lysosomal Storage Diseases/metabolism , Lysosomal Storage Diseases/genetics , Lysosomal Storage Diseases/pathology , Lysosomes/metabolism , Sphingolipids/metabolism , Sphingosine/analogs & derivatives , Sphingosine/metabolismABSTRACT
Mutations in the orphan transporter MFSD7c (also known as Flvcr2), are linked to Fowler syndrome. Here, we used Mfsd7c knockout (Mfsd7c-/-) mice and cell-based assays to reveal that MFSD7c is a choline transporter at the blood-brain barrier (BBB). We performed comprehensive metabolomics analysis and detected differential changes of metabolites in the brains and livers of Mfsd7c-/-embryos. Particularly, we found that choline-related metabolites were altered in the brains but not in the livers of Mfsd7c-/- embryos. Thus, we hypothesized that MFSD7c regulates the level of choline in the brain. Indeed, expression of human MFSD7c in cells significantly increased choline uptake. Interestingly, we showed that choline uptake by MFSD7c is greatly increased by choline-metabolizing enzymes, leading us to demonstrate that MFSD7c is a facilitative transporter of choline. Furthermore, single-cell patch clamp analysis showed that the import of choline by MFSD7c is electrogenic. Choline transport function of MFSD7c was shown to be conserved in vertebrates, but not in yeasts. We demonstrated that human MFSD7c is a functional ortholog of HNM1, the yeast choline importer. We also showed that several missense mutations identified in patients exhibiting Fowler syndrome had abolished or reduced choline transport activity. Mice lacking Mfsd7c in endothelial cells of the central nervous system suppressed the import of exogenous choline from blood but unexpectedly had increased choline levels in the brain. Stable-isotope tracing study revealed that MFSD7c was required for exporting choline derived from lysophosphatidylcholine in the brain. Collectively, our work identifies MFSD7c as a choline exporter at the BBB and provides a foundation for future work to reveal the disease mechanisms of Fowler syndrome.
Subject(s)
Blood-Brain Barrier , Endothelial Cells , Polycystic Ovary Syndrome , Urination Disorders , Animals , Humans , Mice , Biological Transport , Brain , CholineABSTRACT
Vaccination against COVID-19 has been the main strategy used by most countries to limit the spread of the virus. However, vaccine uptake has been low in Africa, leading to the implementation of several interventions in order to improve vaccine coverage. This study was conducted due to the lack of information about COVID-19 vaccine coverage and the factors associated with vaccine hesitancy. This cross-sectional study was carried out in Kinshasa city using multi-stage random sampling. A total of 2160 households were included in this study. The data were analyzed using Stata 17 software. The means and standard deviations were computed for continuous data that followed a normal distribution, whereas proportions together with their 95% confidence intervals (CIs) were computed for categorical variables. The connections between dependent variables and each independent variable were tested using either Pearson's chi-square test or Fisher's exact test. The logistic regression method was employed to determine the factors that are linked to hesitation in obtaining the COVID-19 immunization. The majority of respondents were aged between 25 and 34 and 35 and 49 (28.9%). During this study, 15% (95% CI [13.25-17.9]) of respondents had received at least one dose of the COVID-19 vaccine. The prevalence of vaccine hesitancy was 67% (CI95%:64.9-69.1). Among the reasons given for refusing to be vaccinated, most respondents cited concerns about the vaccine being unsafe or causing adverse reactions (45%). Among the reasons given for accepting the vaccine, 26% thought that the vaccine prevented superinfection. The factors associated with hesitancy toward the COVID-19 vaccine were female gender, an age of less than 35 years, and living in non-slum households. Despite the interventions implemented across the country, the reluctance to be vaccinated remains a problem; this could lead to poor health outcomes, especially among the elderly and those with pre-existing conditions. It is important to step up awareness-raising campaigns in the community in order to increase the uptake of vaccination.
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The binding of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein to the host cell receptor angiotensin-converting enzyme 2 (ACE2) is the first step in human viral infection. Therefore, understanding the mechanism of interaction between RBD and ACE2 at the molecular level is critical for the prevention of COVID-19, as more variants of concern, such as Omicron, appear. Recently, atomic force microscopy has been applied to characterize the free energy landscape of the RBD-ACE2 complex, including estimation of the distance between the transition state and the bound state, xu. Here, using a coarse-grained model and replica-exchange umbrella sampling, we studied the free energy landscape of both the wild type and Omicron subvariants BA.1 and XBB.1.5 interacting with ACE2. In agreement with experiment, we find that the wild type and Omicron subvariants have similar xu values, but Omicron binds ACE2 more strongly than the wild type, having a lower dissociation constant KD.
Subject(s)
COVID-19 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Humans , Angiotensin-Converting Enzyme 2 , Mutation , Protein BindingABSTRACT
Rates of contralateral mastectomy (CM) among patients with unilateral breast cancer have been increasing in the United States. In this Society of Surgical Oncology position statement, we review the literature addressing the indications, risks, and benefits of CM since the society's 2017 statement. We held a virtual meeting to outline key topics and then conducted a literature search using PubMed to identify relevant articles. We reviewed the articles and made recommendations based on group consensus. Patients consider CM for many reasons, including concerns regarding the risk of contralateral breast cancer (CBC), desire for improved cosmesis and symmetry, and preferences to avoid ongoing screening, whereas surgeons primarily consider CBC risk when making a recommendation for CM. For patients with a high risk of CBC, CM reduces the risk of new breast cancer, however it is not known to convey an overall survival benefit. Studies evaluating patient satisfaction with CM and reconstruction have yielded mixed results. Imaging with mammography within 12 months before CM is recommended, but routine preoperative breast magnetic resonance imaging is not; there is also no evidence to support routine postmastectomy imaging surveillance. Because the likelihood of identifying an occult malignancy during CM is low, routine sentinel lymph node surgery is not recommended. Data on the rates of postoperative complications are conflicting, and such complications may not be directly related to CM. Adjuvant therapy delays due to complications have not been reported. Surgeons can reduce CM rates by encouraging shared decision making and informed discussions incorporating patient preferences.
Subject(s)
Breast Neoplasms , Surgical Oncology , Unilateral Breast Neoplasms , Humans , Female , Mastectomy/methods , Breast Neoplasms/pathology , Unilateral Breast Neoplasms/surgery , Medical OncologyABSTRACT
Ultra-wide-field fundus imaging (UFI) provides comprehensive visualization of crucial eye components, including the optic disk, fovea, and macula. This in-depth view facilitates doctors in accurately diagnosing diseases and recommending suitable treatments. This study investigated the application of various deep learning models for detecting eye diseases using UFI. We developed an automated system that processes and enhances a dataset of 4697 images. Our approach involves brightness and contrast enhancement, followed by applying feature extraction, data augmentation and image classification, integrated with convolutional neural networks. These networks utilize layer-wise feature extraction and transfer learning from pre-trained models to accurately represent and analyze medical images. Among the five evaluated models, including ResNet152, Vision Transformer, InceptionResNetV2, RegNet and ConVNext, ResNet152 is the most effective, achieving a testing area under the curve (AUC) score of 96.47% (with a 95% confidence interval (CI) of 0.931-0.974). Additionally, the paper presents visualizations of the model's predictions, including confidence scores and heatmaps that highlight the model's focal points-particularly where lesions due to damage are evident. By streamlining the diagnosis process and providing intricate prediction details without human intervention, our system serves as a pivotal tool for ophthalmologists. This research underscores the compatibility and potential of utilizing ultra-wide-field images in conjunction with deep learning.
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Determining the risk factors for severe disease and death among hospitalized Covid-19 patients is critical to optimize health outcomes and health services efficiency, especially in resource-constrained and humanitarian settings. This study aimed to identify the predictors of mortality of Covid-19 patients in North Kivu province in the Democratic Republic of Congo.A retrospective cohort study was conducted in 6 Covid-19 treatment centers in the city of Butembo from 1 January to 31 December 2021. The time to event (death), the outcome variable, was visualized by Kaplan-Meier curves and the log-rank test was used to confirm differences in trends. Cox regression was used for all the predictors in the bivariate analysis and multivariate analysis was done using predictors found statistically significant in the bivariate analysis. The following variables were considered for inclusion to the Cox regression model: Age, Sex, Disease length, Treatment site, History of at least one co-morbidity, Body mass index, Stage according to SpO2 and the NEWS-modified score.Among the 303 participants (mean age of 53 years), the fatality rate was 33.8 deaths per 1000 patient-days. Four predictors were independently associated with inpatient death: age category (≥ 60 years) (adjusted HR: 9.90; 95% CI: 2.68-36.27), presence of at least one comorbidity (adjusted HR: 11.39; 95% CI: 3.19-40.71); duration of illness of > 5 days before hospitalization (adjusted HR:1.70, 95% CI: 1.04-2.79) and peripheral capillary oxygen saturation (SpO2) < 90% (adjusted HR = 14.02, 95% CI: 2.23-88.32). In addition to advanced age, comorbidity, and length of disease before hospitalization, ambient air SpO2 measured by healthcare providers using low-tech, affordable and relatively accessible pulse oximetry could inform the care pathways of Covid-19 inpatients in resource-challenged health systems in humanitarian settings.
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Many homodimeric enzymes tune their functions by exploiting either negative or positive cooperativity between subunits. In the SARS-CoV-2 Main protease (Mpro) homodimer, the latter has been suggested by symmetry in most of the 500 reported protease/ligand complex structures solved by macromolecular crystallography (MX). Here we apply the latter to both covalent and noncovalent ligands in complex with Mpro. Strikingly, our experiments show that the occupation of both active sites of the dimer originates from an excess of ligands. Indeed, cocrystals obtained using a 1:1 ligand/protomer stoichiometry lead to single occupation only. The empty binding site exhibits a catalytically inactive geometry in solution, as suggested by molecular dynamics simulations. Thus, Mpro operates through negative cooperativity with the asymmetric activity of the catalytic sites. This allows it to function with a wide range of substrate concentrations, making it resistant to saturation and potentially difficult to shut down, all properties advantageous for the virus' adaptability and resistance.
Subject(s)
COVID-19 , Humans , SARS-CoV-2/metabolism , Ligands , Coronavirus 3C Proteases/metabolism , Molecular Dynamics Simulation , Protease Inhibitors/chemistry , Molecular Docking SimulationABSTRACT
This study aimed to investigate the co-infection and genetic characteristics of Porcine circoviruses in PMWS-affected pigs in five commercial farrow-to-finish swine farms in Vietnam. By the end of 2022, the percentage of PMWS-affected pigs in these farms has increased significantly compared to previous years. The lymph node samples from ten PMWS typical cases were randomly collected to test for the presence of PRRSV, PCV2, PCV3 and PCV4. While PRRSV and PCV4 were not found in these cases, 10 and 3 out of 10 samples were positive for PCV2 and PCV3, respectively. Three farms in the study showed the co-infection of PCV2 and PCV3 in affected pigs. Besides, all PCV-positive samples were sequenced to evaluate genetic characterization of PCVs in PMWS-affected cases. Phylogenetic analysis showed that all PCV3 strains in the study were clustered into PCV3b genotype. 8 out of 10 PCV2 strains belonged to PCV2d genotype while the remaining two strains belonged to PCV2b genotypes. Two farms had co-circulation of PCV2b and PCV2d genotypes in two different age groups of pigs, which is reported for the first time in Vietnam. Several amino acid substitutions were identified in important antigenic regions in the capsid protein of the PCV2 field strains compared to vaccine strains. Taken together, the results showed the high co-prevalence of PCV3 and PCV2, and the wide genetic diversity of PCV2 field and vaccine strains may be the cause of the increased PMWS situation in these pig farms. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-023-00849-4.
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MFSD7b belongs to the Major Facilitator Superfamily of transporters that transport small molecules. Two isoforms of MFSD7b have been identified and they are reported to be heme exporters that play a crucial role in maintaining the cytosolic and mitochondrial heme levels, respectively. Mutations of MFSD7b (also known as FLVCR1) have been linked to retinitis pigmentosa, posterior column ataxia, and hereditary sensory and autonomic neuropathy. Although MFSD7b functions have been linked to heme detoxification by exporting excess heme from erythroid cells, it is ubiquitously expressed with a high level in the kidney, gastrointestinal tract, lungs, liver, and brain. Here, we showed that MFSD7b functions as a facilitative choline transporter. Expression of MFSD7b slightly but significantly increased choline import, while its knockdown reduced choline influx in mammalian cells. The influx of choline transported by MFSD7b is dependent on the expression of choline metabolizing enzymes such as choline kinase (CHKA) and intracellular choline levels, but it is independent of gradient of cations. Additionally, we showed that choline transport function of Mfsd7b is conserved from fly to man. Employing our transport assays, we showed that missense mutations of MFSD7b caused reduced choline transport functions. Our results show that MFSD7b functions as a facilitative choline transporter in mammalian cells.
Subject(s)
Choline , Membrane Transport Proteins , Mutation, Missense , Animals , Humans , Choline/metabolism , Heme , Mammals , Membrane Transport Proteins/geneticsABSTRACT
Background Chest radiography remains the most common radiologic examination, and interpretation of its results can be difficult. Purpose To explore the potential benefit of artificial intelligence (AI) assistance in the detection of thoracic abnormalities on chest radiographs by evaluating the performance of radiologists with different levels of expertise, with and without AI assistance. Materials and Methods Patients who underwent both chest radiography and thoracic CT within 72 hours between January 2010 and December 2020 in a French public hospital were screened retrospectively. Radiographs were randomly included until reaching 500 radiographs, with about 50% of radiographs having abnormal findings. A senior thoracic radiologist annotated the radiographs for five abnormalities (pneumothorax, pleural effusion, consolidation, mediastinal and hilar mass, lung nodule) based on the corresponding CT results (ground truth). A total of 12 readers (four thoracic radiologists, four general radiologists, four radiology residents) read half the radiographs without AI and half the radiographs with AI (ChestView; Gleamer). Changes in sensitivity and specificity were measured using paired t tests. Results The study included 500 patients (mean age, 54 years ± 19 [SD]; 261 female, 239 male), with 522 abnormalities visible on 241 radiographs. On average, for all readers, AI use resulted in an absolute increase in sensitivity of 26% (95% CI: 20, 32), 14% (95% CI: 11, 17), 12% (95% CI: 10, 14), 8.5% (95% CI: 6, 11), and 5.9% (95% CI: 4, 8) for pneumothorax, consolidation, nodule, pleural effusion, and mediastinal and hilar mass, respectively (P < .001). Specificity increased with AI assistance (3.9% [95% CI: 3.2, 4.6], 3.7% [95% CI: 3, 4.4], 2.9% [95% CI: 2.3, 3.5], and 2.1% [95% CI: 1.6, 2.6] for pleural effusion, mediastinal and hilar mass, consolidation, and nodule, respectively), except in the diagnosis of pneumothorax (-0.2%; 95% CI: -0.36, -0.04; P = .01). The mean reading time was 81 seconds without AI versus 56 seconds with AI (31% decrease, P < .001). Conclusion AI-assisted chest radiography interpretation resulted in absolute increases in sensitivity for all radiologists of various levels of expertise and reduced the reading times; specificity increased with AI, except in the diagnosis of pneumothorax. © RSNA, 2023 Supplemental material is available for this article.
Subject(s)
Lung Diseases , Pleural Effusion , Pneumothorax , Humans , Male , Female , Middle Aged , Artificial Intelligence , Retrospective Studies , Radiography, Thoracic/methods , Radiography , Sensitivity and Specificity , RadiologistsABSTRACT
Strongyloidiasis is a helminth infection affecting 613.9 million people annually, mainly in the tropics and subtropics. The reported seroprevalence in the United States is 4% with most of the cases reported in immigrants. Human T-lympho-tropic virus 1 (HTLV-1) infections, hypogammaglobulinemia, immunosuppressant use - particularly steroid use, alcoholism, and malnutrition have been associated with an increased risk of strongyloidiasis. Recently, cases of strongyloidiasis hyperinfection syndrome have been described in coronavirus disease 2019 (COVID-19) patients treated with steroids as well. This brief review discusses the epidemiology, clinical features, management, and prevention of strongyloidiasis including some facts about the infection in pregnancy, transplant recipients, and COVID-19 patients. We conducted an online search using the PubMed, Scopus, and Google Scholar databases. Strongyloidiasis can be asymptomatic or present with mild symptoms. Strongyloides stercoralis is known to cause autoinfection. In immunocompromised individuals, it can present with severe symptoms, hyperinfection, or disseminated disease. Reported mortality in cases of disseminated Strongyloidiasis is 87.1%. Serology and detection of larvae in stool by direct microscopy are the most commonly used methods to diagnose strongyloidiasis. The drug of choice for the treatment is ivermectin. However, the use of ivermectin in human pregnancy is not well studied, and its teratogenic risks are unknown. Proactive screening of strongyloidiasis is necessary in immunocompromised individuals to prevent severe disease.