Cascaded Multi-path Shortcut Diffusion Model for Medical Image Translation.

Image-to-image translation is a vital component in medical imaging processing, with many uses in a wide range of imaging modalities and clinical scenarios. Previous methods include Generative Adversarial Networks (GANs) and Diffusion Models (DMs), which offer realism but suffer from instability and lack uncertainty estimation. Even though both GAN and DM methods have individually exhibited their capability in medical image translation tasks, the potential of combining a GAN and DM to further improve translation performance and to enable uncertainty estimation remains largely unexplored. In this work, we address these challenges by proposing a Cascade Multi-path Shortcut Diffusion Model (CMDM) for high-quality medical image translation and uncertainty estimation. To reduce the required number of iterations and ensure robust performance, our method first obtains a conditional GAN-generated prior image that will be used for the efficient reverse translation with a DM in the subsequent step. Additionally, a multi-path shortcut diffusion strategy is employed to refine translation results and estimate uncertainty. A cascaded pipeline further enhances translation quality, incorporating residual averaging between cascades. We collected three different medical image datasets with two sub-tasks for each dataset to test the generalizability of our approach. Our experimental results found that CMDM can produce high-quality translations comparable to state-of-the-art methods while providing reasonable uncertainty estimations that correlate well with the translation error.

Synergistically improved cardiovascular outcomes in type 2 diabetes mellitus patients with combined treatment of SGLT-2 inhibitors and pioglitazone.

Background: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have cardiovascular (CV) benefits, particularly in reducing the risk of heart failure (HF). Pioglitazone (Pio) has shown potential in decreasing the risks of recurrent stroke, non-fatal myocardial infarction (MI), and all-cause mortality but increasing risks of HF. Our study aimed to examine the synergistic effects on CV outcomes in patients with type 2 diabetes mellitus (T2DM) who received the combined treatment of SGLT2i and Pio. Materials and methods: A total of 117,850 patients with T2DM and without a history of HF were selected as the observational study cohort from the Chang Gung Research Database (CGRD) in Taiwan between January 1, 2016, and December 31, 2019. The primary composite outcome was 4-point major adverse CV events (4P-MACE), including CV death, non-fatal MI, non-fatal ischemic stroke, and hospitalization for HF. The study was divided into four groups: a combined treatment group in which SGLT2i and Pio were used, two individual groups in which SGLT2i or Pio was used separately, and a reference group (non-study drugs). Results: Combined treatment of SGLT2i and Pio had the lowest risk of 4P-MACE (adjusted hazard ratio [aHR], 0.66; 95% confidence interval [CI], 0.54-0.80) compared with the reference group after a mean follow-up of 2.2 years. There was no significant difference in risks of hospitalization for HF (adjusted subdistribution hazard ratio, 0.73; 95% CI, 0.49-1.07) compared with the reference group. Conclusions: In T2DM patients without HF, the combined treatment with SGLT2i and Pio may synergistically provide CV benefits without increasing risks of HF.

HiRegEx: Interactive Visual Query and Exploration of Multivariate Hierarchical Data.

When using exploratory visual analysis to examine multivariate hierarchical data, users often need to query data to narrow down the scope of analysis. However, formulating effective query expressions remains a challenge for multivariate hierarchical data, particularly when datasets become very large. To address this issue, we develop a declarative grammar, HiRegEx (Hierarchical data Regular Expression), for querying and exploring multivariate hierarchical data. Rooted in the extended multi-level task topology framework for tree visualizations (e-MLTT), HiRegEx delineates three query targets (node, path, and subtree) and two aspects for querying these targets (features and positions), and uses operators developed based on classical regular expressions for query construction. Based on the HiRegEx grammar, we develop an exploratory framework for querying and exploring multivariate hierarchical data and integrate it into the TreeQueryER prototype system. The exploratory framework includes three major components: top-down pattern specification, bottom-up data-driven inquiry, and context-creation data overview. We validate the expressiveness of HiRegEx with the tasks from the e-MLTT framework and showcase the utility and effectiveness of TreeQueryER system through a case study involving expert users in the analysis of a citation tree dataset.

Prompt-driven Latent Domain Generalization for Medical Image Classification.

Deep learning models for medical image analysis easily suffer from distribution shifts caused by dataset artifact bias, camera variations, differences in the imaging station, etc., leading to unreliable diagnoses in real-world clinical settings. Domain generalization (DG) methods, which aim to train models on multiple domains to perform well on unseen domains, offer a promising direction to solve the problem. However, existing DG methods assume domain labels of each image are available and accurate, which is typically feasible for only a limited number of medical datasets. To address these challenges, we propose a unified DG framework for medical image classification without relying on domain labels, called Prompt-driven Latent Domain Generalization (PLDG). PLDG consists of unsupervised domain discovery and prompt learning. This framework first discovers pseudo domain labels by clustering the bias-associated style features, then leverages collaborative domain prompts to guide a Vision Transformer to learn knowledge from discovered diverse domains. To facilitate cross-domain knowledge learning between different prompts, we introduce a domain prompt generator that enables knowledge sharing between domain prompts and a shared prompt. A domain mixup strategy is additionally employed for more flexible decision margins and mitigates the risk of incorrect domain assignments. Extensive experiments on three medical image classification tasks and one debiasing task demonstrate that our method can achieve comparable or even superior performance than conventional DG algorithms without relying on domain labels. Our code is publicly available at https://github.com/SiyuanYan1/PLDG/tree/main.

Corrigendum: Nitric oxide alleviated high salt-induced cardiomyocyte apoptosis and autophagy independent of blood pressure in rats.

[This corrects the article DOI: 10.3389/fcell.2021.646575.].

Attenuation of renal fibrosis in mice due to lack of bombesin receptor-activated protein homologue.

Bombesin receptor-activated protein (BRAP), encoded by the C6orf89 gene in humans, is expressed in various cells with undefined functions. BC004004, the mouse homologue of C6orf89, has been shown to play a role in bleomycin-induced pulmonary fibrosis through the use of a BC004004 gene knockout mouse (BC004004-/-). In this study, we investigated the potential involvement of BRAP in renal fibrosis using two mouse models: unilateral ureteral obstruction (UUO) and type 2 diabetes mellitus induced by combination of a high-fat diet (HFD) and streptozocin (STZ). BRAP or its homologue was expressed in tubular epithelial cells (TECs) in the kidneys of patients with chronic kidney disease (CKD) and in BC004004+/+ mice. Compared to control mice, BC004004-/- mice exhibited attenuated renal injury and renal fibrosis after UUO or after HFD/STZ treatment. Immunohistochemistry and immunoblot analyses of the kidneys of BC004004+/+ mice after UUO surgery showed a more significant decrease in E-cadherin expression and a more significant increase in both α smooth muscle actin (α-SMA) and vimentin expression compared to BC004004-/- mice. Additionally, stimulation with transforming growth factor-ß1 (TGF-ß1) led to a more significant decrease in E-cadherin expression and a more significant increase in α-SMA and vimentin expression in isolated TECs from BC004004+/+ than in those from BC004004-/- mice. These results suggest that an enhanced epithelial-mesenchymal transition (EMT) process occurred in TECs in BC004004+/+ mice during renal injury, which might contribute to renal fibrosis. The loss of the BRAP homologue in BC004004-/- mice suppressed EMT activation in kidneys and contributed to the suppression of fibrosis during renal injury.

Adsorption and Potential CO Gas-Sensing Performance of the Fe-Doped Ti2CO2-MXenes: A First-Principles Study.

The adsorption behaviors and electronic properties of five gas molecules (CO, H2O, NH3, NO, and C2H6O) on the intrinsic Ti2CO2 and Fe-doped Ti2CO2 were calculated and studied based on first principles. The adsorption height, bond length change, adsorption energy, charge transfer, band structure, differential charge, work function, and recovery time of the two gas adsorption systems were discussed, and their sensing performance was evaluated. The results show that the CO gas molecules have the best adsorption energy and charge transfer on Ti2CO2 modified by the Fe atom (Ti2CO2-Fe). The electrical conductivity obviously increases with the decrease of the band gap, which changes from semiconductor to conductor behavior. The reduction of the work function in the Ti2CO2-Fe system weakens the binding of the electron, which improves the electron flow between the substrate and the gas molecules. In addition, the Ti2CO2-Fe system with H2O molecule participation remained the best adsorption effect on CO gas, and the fast recovery time was 625 s at 398 K. Therefore, Ti2CO2-Fe is a prospective material for the advancement of CO gas-sensitive sensors.

A hot-emitter transistor based on stimulated emission of heated carriers.

Hot-carrier transistors are a class of devices that leverage the excess kinetic energy of carriers. Unlike regular transistors, which rely on steady-state carrier transport, hot-carrier transistors modulate carriers to high-energy states, resulting in enhanced device speed and functionality. These characteristics are essential for applications that demand rapid switching and high-frequency operations, such as advanced telecommunications and cutting-edge computing technologies1-5. However, the traditional mechanisms of hot-carrier generation are either carrier injection6-11 or acceleration12,13, which limit device performance in terms of power consumption and negative differential resistance14-17. Mixed-dimensional devices, which combine bulk and low-dimensional materials, can offer different mechanisms for hot-carrier generation by leveraging the diverse potential barriers formed by energy-band combinations18-21. Here we report a hot-emitter transistor based on double mixed-dimensional graphene/germanium Schottky junctions that uses stimulated emission of heated carriers to achieve a subthreshold swing lower than 1 millivolt per decade beyond the Boltzmann limit and a negative differential resistance with a peak-to-valley current ratio greater than 100 at room temperature. Multi-valued logic with a high inverter gain and reconfigurable logic states are further demonstrated. This work reports a multifunctional hot-emitter transistor with significant potential for low-power and negative-differential-resistance applications, marking a promising advancement for the post-Moore era.

Associations between DEET, Organophosphorus Insecticides, and Handgrip Strength in Diabetes: An NHANES Analysis.

INTRODUCTION: Sarcopenia and diabetes mellitus (DM) have been shown to be related. It has been demonstrated that pesticides/insecticides are linked to various health issues, including DM. This study investigated the relationships between exposure to pesticides/insecticides and muscle strength among community-dwelling DM patients in a national sample of the United States (US). METHODS: Data from the 2011-2012 and 2013-2014 U.S. National Health and Nutrition Examination Survey (NHANES) on people aged 20 years with diabetes were retrieved. A digital dynamometer was used to quantify handgrip strength, and urine pesticide concentrations were determined through laboratory testing. Regression models were used to investigate the relationship between pesticide/insecticide exposure and handgrip strength. RESULTS: After weighting, the data from 412 NHANES participants represented 6,696,865 U.S. inhabitants. The mean age of the participants was 58.8 years. High para-nitrophenol levels (tertile 3 vs. tertile 1) were shown to be associated with lower handgrip strength in both males (aBeta = -7.25, 95% CI: -11.25, -3.25) and females (aBeta = -3.73, 95% CI: -6.89, -0.56). Further, females with elevated 2-isopropyl-4-methyl-pyrimidinol had decreased handgrip strength. Desethyl hydroxy N, N-diethyl-m-toluamide (DEET) was inversely related to handgrip strength in men aged ≥60 years. DEET acid and para-nitrophenol were inversely correlated to handgrip strength in women over 60 years. CONCLUSIONS: This study has linked certain pesticides/insecticides to decreased muscle strength in people with diabetes. Para-nitrophenol, in particular, is negatively related to muscular strength in both males and females, and 2-isopropyl-4-methyl-pyrimidinol is inversely related to muscle strength in females.

Caught Between a Radiation Oncology Case Rate (ROCR) and a Hard Place: Improving Proposed Radiation Oncology Alternative Payment Models.

PURPOSE: The Radiation Oncology Case Rate (ROCR) aims to shift radiation reimbursement from fee-for-service (FFS) to bundled payments, which would decouple fractionation from reimbursement in the United States. This study compares historical reimbursement rates from 3 large centers and a national Medicare sample with proposed base rates from ROCR. It also tests the impact of methodological inclusion of treatment and disease characteristics to determine if any variables are associated with greater rate differences that may lead to inequitable reimbursement. METHODS AND MATERIALS: Using Mayo Clinic electronic medical record data from 2017 to 2020 and part B claims from the Medicare 5% research identifiable files, episodic 90-day historical reimbursement rates for 15 cancer types were calculated per the ROCR payment methodology. Mayo Clinic reimbursement rates were stratified by disease and treatment characteristics and multiple linear regression was performed to assess the association of these variables on historical episode reimbursement rates. RESULTS: From Mayo Clinic, 3498 patient episodes were included and 480,526 from the research identifiable files. From both data sets, 25% of brain metastases and 13% of bone metastases episodes included ≥2 treatment courses with an average of 51 days between courses. Accounting for all 15 cancer types, ROCR base rates resulted in an average -2.4% and -2.9% reduction in rates for Mayo Clinic and the research identifiable files respectively compared with historical reimbursement. On multivariate analysis of Mayo Clinic data, treatment intent (curative vs palliative) was associated with higher historical reimbursement (+$477 to +$7417; P ≤.05) for 12 out of 12 applicable cancer types. Stage (III-IV vs I-II) was associated with higher historical reimbursement (+$1169 to +$3917; P ≤ .05) for 8 out of 12 applicable cancer types. CONCLUSIONS: Our data suggest ROCR base rates introduce an average ≤3% reimbursement rate decrease compared with historical FFS reimbursement per cancer type, which could produce the Medicare savings required for congressional approval of ROCR. Estimating comparisons with future FFS reimbursement would require consideration of additional factors such as the increased utilization of hypofractionation, proposed FFS rate cuts, and inflationary updates. A distinct rate and shortened episode duration (≤30 days) should be considered for palliative episodes. Applying a base rate modifier per cancer stage may mitigate disproportionate reductions in reimbursement for facilities with a higher volume of curative advanced-stage patients such as freestanding centers in rural settings.

Chloride intracellular channel 4 participates in the regulation of lipopolysaccharide-induced inflammatory responses in human bronchial epithelial cells.

The airway epithelium is located at the interactional boundary between the external and internal environments of the organism and is often exposed to harmful environmental stimuli. Inflammatory response that occurs after airway epithelial stress is the basis of many lung and systemic diseases. Chloride intracellular channel 4 (CLIC4) is abundantly expressed in epithelial cells. The purpose of this study was to investigate whether CLIC4 is involved in the regulation of lipopolysaccharide (LPS)-induced inflammatory response in airway epithelial cells and to clarify its potential mechanism. Our results showed that LPS induced inflammatory response and decreased CLIC4 levels in vivo and in vitro. CLIC4 silencing aggravated the inflammatory response in epithelial cells, while overexpression of CLIC4 combined with LPS exposure significantly decreased the inflammatory response compared with cells exposed to LPS without CLIC4 overexpression. By labeling intracellular chloride ions with chloride fluorescent probe MQAE, we showed that CLIC4 mediated intracellular chloride ion-regulated LPS-induced cellular inflammatory response.

Aging in chronic lung disease: Will anti-aging therapy be the key to the cure?

Chronic lung disease is the third leading cause of death globally, imposing huge burden of death, disability and healthcare costs. However, traditional pharmacotherapy has relatively limited effects in improving the cure rate and reducing the mortality of chronic lung disease. Thus, new treatments are urgently needed for the prevention and treatment of chronic lung disease. It is particularly noteworthy that, multiple aging-related phenotypes were involved in the occurrence and development of chronic lung disease, such as blocked proliferation, telomere attrition, mitochondrial dysfunction, epigenetic alterations, altered nutrient perception, stem cell exhaustion, chronic inflammation, etc. Consequently, senescent cells induce a series of pathological changes in the lung, such as immune dysfunction, airway remodeling, oxidative stress and regenerative dysfunction, which is a critical issue that needs special attention in chronic lung diseases. Therefore, anti-aging interventions may bring new insights into the treatment of chronic lung diseases. In this review, we elaborate the involvement of aging in chronic lung disease and further discuss the application and prospects of anti-aging therapy.

Efficacy of the tetravalent protein COVID-19 vaccine, SCTV01E: a phase 3 double-blind, randomized, placebo-controlled trial.

Evolution of SARS-CoV-2 variants emphasizes the need for multivalent vaccines capable of simultaneously targeting multiple strains. SCTV01E is a tetravalent COVID-19 vaccine derived from the spike protein of SARS-CoV-2 variants Alpha, Beta, Delta, and Omicron BA.1. In this double-blinded placebo-controlled pivotal efficacy trial (NCT05308576), the primary endpoint was vaccine efficacy (VE) against COVID-19 seven days post-vaccination in individuals without recent infection. Other endpoints included evaluating safety, immunogenicity, and the VE against all SARS-CoV-2 infections in individuals meeting the study criteria. Between December 26, 2022, and January 15, 2023, 9,223 individuals were randomized at a 1:1 ratio to receive SCTV01E or a placebo. SCTV01E showed a VE of 69.4% (95% CI: 50.6, 81.0) 7 days post-vaccination, with 75 cases in the placebo group and 23 in the SCTV01E group for the primary endpoint. VEs were 79.7% (95% CI: 51.0, 91.6) and 82.4% (95% CI: 57.9, 92.6), respectively, for preventing symptomatic infection and all SARS-CoV-2 infections 14 days post-vaccination. SCTV01E elicited a 25.0-fold higher neutralizing antibody response against Omicron BA.5 28 days post-vaccination compared to placebo. Reactogenicity was generally mild and transient, with no reported vaccine-related SAE, adverse events of special interest (AESI), or deaths. The trial aligned with the shift from dominant variants BA.5 and BF.7 to XBB, suggesting SCTV01E as a potential vaccine alternative effective against present and future variants.

Association between Time to Emergent Surgery and Outcomes in Trauma Patients: A 10-Year Multicenter Study.

Background: Research on the impact of reduced time to emergent surgery in trauma patients has yielded inconsistent results. Therefore, this study investigated the relationship between waiting emergent surgery time (WEST) and outcomes in trauma patients. Methods: This retrospective, multicenter study used data from the Tzu Chi Hospital trauma database. The primary clinical outcomes were in-hospital mortality, intensive care unit (ICU) admission, and prolonged hospital length of stay (LOS) of ≥30 days. Results: A total of 15,164 patients were analyzed. The median WEST was 444 min, with an interquartile range (IQR) of 248-848 min for all patients. Patients who died in the hospital had a shorter median WEST than did those who survived (240 vs. 446 min, p < 0.001). Among the trauma patients with a WEST of <2 h, the median time was 79 min (IQR = 50-100 min). No significant difference in WEST was observed between the survival and mortality groups for patients with a WEST of <120 min (median WEST: 85 vs. 78 min, p < 0.001). Multivariable logistic regression analysis revealed that WEST was not associated with an increased risk of in-hospital mortality (adjusted odds ratio [aOR] = 1.05, 95% confidence interval [CI] = 0.17-6.35 for 30 min ≤ WEST < 60 min; aOR = 1.12, 95% CI = 0.22-5.70 for 60 min ≤ WEST < 90 min; and aOR = 0.60, 95% CI = 0.13-2.74 for WEST ≥ 90 min). Conclusions: Our findings do not support the "golden hour" concept because no association was identified between the time to definitive care and in-hospital mortality, ICU admission, and prolonged hospital stay of ≥30 days.

The microgeo: an R package rapidly displays the biogeography of soil microbial community traits on maps.

Many R packages provide statistical approaches for elucidating the diversity of soil microbes, yet they still struggle to visualize microbial traits on a geographical map. This creates challenges in interpreting microbial biogeography on a regional scale, especially when the spatial scale is large or the distribution of sampling sites is uneven. Here, we developed a lightweight, flexible, and user-friendly R package called microgeo. This package integrates many functions involved in reading, manipulating, and visualizing geographical boundary data; downloading spatial datasets; and calculating microbial traits and rendering them onto a geographical map using grid-based visualization, spatial interpolation, or machine learning. Using this R package, users can visualize any trait calculated by microgeo or other tools on a map and can analyze microbiome data in conjunction with metadata derived from a geographical map. In contrast to other R packages that statistically analyze microbiome data, microgeo provides more-intuitive approaches in illustrating the biogeography of soil microbes on a large geographical scale, serving as an important supplement to statistically driven comparisons and facilitating the biogeographic analysis of publicly accessible microbiome data at a large spatial scale in a more convenient and efficient manner. The microgeo R package can be installed from the Gitee (https://gitee.com/bioape/microgeo) and GitHub (https://github.com/ChaonanLi/microgeo) repositories. Detailed tutorials for the microgeo R package are available at https://chaonanli.github.io/microgeo.

Incidence of Carotid Blowout Syndrome in Patients with Head and Neck Cancer after Radiation Therapy: A Cohort Study.

Carotid blowout syndrome (CBS) is a rare yet life-threatening complication that occurs after radiation therapy (RT). This study aimed to determine the incidence of CBS in patients with head and neck cancer (HNC) undergoing contemporary RT and to explore potential discrepancies in the risk of CBS between nasopharyngeal cancer (NPC) and non-NPC patients. A total of 1084 patients with HNC who underwent RT between 2013 and 2023 were included in the study. All patients were under regular follow-ups at the radio-oncology department, and underwent annual contrast-enhanced computed tomography and/or magnetic resonance imaging for cancer recurrence surveillance. Experienced neuroradiologists and vascular neurologists reviewed the recruited patients' images. Patients were further referred to the neurology department for radiation vasculopathy evaluation. The primary outcome of this study was CBS. Patients were categorized into NPC and non-NPC groups and survival analysis was employed to compare the CBS risk between the two groups. A review of the literature on CBS incidence was also conducted. Among the enrolled patients, the incidence of CBS in the HNC, NPC, and non-NPC groups was 0.8%, 0.9%, and 0.7%, respectively. Kaplan-Meier analysis revealed no significant difference between the NPC and non-NPC groups (p = 0.34). Combining the findings for our cohort with those of previous studies revealed that the cumulative incidence of CBS in patients with HNC is 5% (95% CI = 3-7%) after both surgery and RT, 4% (95% CI = 2-6%) after surgery alone, and 5% (95% CI = 3-7%) after RT alone. Our findings indicate a low incidence of CBS in patients with HNC undergoing contemporary RT. Patients with NPC may have a CBS risk close to that of non-NPC patients. However, the low incidence of CBS could be a potentially cause of selection bias and underestimation bias.

Polymorphism of CYP3A4*18 is associated with anti-tuberculosis drug-induced hepatotoxicity.

Aim: The association between cytochrome P450 (CYP) gene polymorphisms and anti-tuberculosis drug-induced hepatotoxicity (ATDH) was investigated in patients with or without pre-existing liver diseases (PLD). Materials & methods: We followed 164 tuberculosis subjects, 58 with PLD and 106 without PLD. Polymorphisms in CYP2D6, CYP2C9, CYP2C19, CYP3A4 and CYP3A5 were analyzed using the TaqMan® SNP genotyping assay.Results: The CYP3A4*18 heterozygous genotype was associated with ATDH (OR: 3.24, 95% CI: 1.06-9.86) regardless of PLD presence. Among subjects without PLD, CYP3A4*18 heterozygotes had significantly higher ATDH risk (OR: 9.10, 95% CI: 1.56-53.16). Conversely, in the PLD group, CYP3A4*18 heterozygotes had lower ATDH risk (OR: 0.21, 95% CI: 0.05-0.98).Conclusion: CYP3A4*18 genotype is linked to ATDH in tuberculosis patients, with differential effects based on PLD presence.

[Box: see text].

Airway epithelial overexpressed cathepsin K induces airway remodelling through epithelial-mesenchymal trophic unit activation in asthma.

BACKGROUND AND PURPOSE: Airway epithelial cells (AECs) regulate the activation of epithelial-mesenchymal trophic units (EMTUs) during airway remodelling through secretion of signalling mediators. However, the major trigger and the intrinsic pathogenesis of airway remodelling is still obscure. EXPERIMENTAL APPROACH: The differing expressed genes in airway epithelia related to airway remodelling were screened and verified by RNA-sequencing and signalling pathway analysis. Then, the effects of increased cathepsin K (CTSK) in airway epithelia on airway remodelling and EMTU activation were identified both in vitro and in vivo, and the molecular mechanism was elucidated in the EMTU model. The potential of CTSK as an an effective biomarker of airway remodelling was analysed in an asthma cohort of differing severity. Finally, an inhibitor of CTSK was administered for potential therapeutic intervention for airway remodelling in asthma. KEY RESULTS: The expression of CTSK in airway epithelia increased significantly along with the development of airway remodelling in a house dust mite (HDM)-stressed asthma model. Increased secretion of CTSK from airway epithelia induced the activation of EMTUs by activation of the PAR2-mediated pathway. Blockade of CTSK inhibited EMTU activation and alleviated airway remodelling as an effective intervention target of airway remodelling. CONCLUSION AND IMPLICATIONS: Increased expression of CTSK in airway epithelia is involved in the development of airway remodelling in asthma through EMTU activation, mediated partly through the PAR2-mediated signalling pathway. CTSK is a potential biomarker for airway remodelling, and may also be a useful intervention target for airway remodelling in asthma patients.

Performance Characteristics of the NeuroEXPLORER, a Next-Generation Human Brain PET/CT Imager.

The collaboration of Yale, the University of California, Davis, and United Imaging Healthcare has successfully developed the NeuroEXPLORER, a dedicated human brain PET imager with high spatial resolution, high sensitivity, and a built-in 3-dimensional camera for markerless continuous motion tracking. It has high depth-of-interaction and time-of-flight resolutions, along with a 52.4-cm transverse field of view (FOV) and an extended axial FOV (49.5 cm) to enhance sensitivity. Here, we present the physical characterization, performance evaluation, and first human images of the NeuroEXPLORER. Methods: Measurements of spatial resolution, sensitivity, count rate performance, energy and timing resolution, and image quality were performed adhering to the National Electrical Manufacturers Association (NEMA) NU 2-2018 standard. The system's performance was demonstrated through imaging studies of the Hoffman 3-dimensional brain phantom and the mini-Derenzo phantom. Initial 18F-FDG images from a healthy volunteer are presented. Results: With filtered backprojection reconstruction, the radial and tangential spatial resolutions (full width at half maximum) averaged 1.64, 2.06, and 2.51 mm, with axial resolutions of 2.73, 2.89, and 2.93 mm for radial offsets of 1, 10, and 20 cm, respectively. The average time-of-flight resolution was 236 ps, and the energy resolution was 10.5%. NEMA sensitivities were 46.0 and 47.6 kcps/MBq at the center and 10-cm offset, respectively. A sensitivity of 11.8% was achieved at the FOV center. The peak noise-equivalent count rate was 1.31 Mcps at 58.0 kBq/mL, and the scatter fraction at 5.3 kBq/mL was 36.5%. The maximum count rate error at the peak noise-equivalent count rate was less than 5%. At 3 iterations, the NEMA image-quality contrast recovery coefficients varied from 74.5% (10-mm sphere) to 92.6% (37-mm sphere), and background variability ranged from 3.1% to 1.4% at a contrast of 4.0:1. An example human brain 18F-FDG image exhibited very high resolution, capturing intricate details in the cortex and subcortical structures. Conclusion: The NeuroEXPLORER offers high sensitivity and high spatial resolution. With its long axial length, it also enables high-quality spinal cord imaging and image-derived input functions from the carotid arteries. These performance enhancements will substantially broaden the range of human brain PET paradigms, protocols, and thereby clinical research applications.

Airway epithelial-derived exosomes induce acute asthma exacerbation after respiratory syncytial virus infection.

Acute asthma exacerbation refers to the progressive deterioration of asthma symptoms that is always triggered by virus infection represented by respiratory syncytial virus (RSV). After RSV infection, exaggerated Th2-mediated pulmonary inflammation is the critical pathological response of asthmatic patients with acute exacerbation. Significantly, airway epithelial cells, being the primary targets of RSV infection, play a crucial role in controlling the pulmonary inflammatory response by releasing airway epithelial cell-derived exosomes (AEC-Exos), which potentially influence the development of asthma. However, the specific role of AEC-Exos in acute asthma exacerbation after RSV infection remains obscure. The purpose of this study was to determine the distinct function of AEC-Exos in exacerbating acute asthma following RSV infection. Blockade of exosomes by GW reduce the enhanced pulmonary inflammation significantly. Specifically, the enhanced Th2 inflammation was induced by AEC-Exos thorough transportation of hsa-miR-155-5p-Sirtuin 1 (SIRT1) pathway during acute asthma exacerbation. Targeted inhibition of hsa-miR-155-5p blocks the exaggerated Th2 inflammation effectively in mice with acute asthma exacerbation. In summary, our study showed that during acute asthma exacerbation after RSV infection, AEC-Exos promote the enhanced Th2 inflammation through transportation of increased hsa-miR-155-5p, which was mediated partly through SIRT1-mediated pathway. hsa-miR-155-5p is a potential biomarker for early prediction of acute asthma exacerbation.