68 Ga-FAPI-04 PET/CT for the Evaluation of Cholangiocarcinoma : Comparison With 18 F-FDG PET/CT and Abdominal 68 Ga-FAPI-04 PET/MR.

PURPOSE: In this study, we evaluated and compared the diagnostic performances of 68 Ga-FAPI-04 PET/CT and 18 F-FDG PET/CT for primary and metastatic cholangiocarcinoma (CCA) lesions. We also investigated the performance of PET/MR for visualizing and characterizing CCA and liver metastasis lesions. PATIENTS AND METHODS: Forty-four patients with suspected CCA were recruited and underwent 68 Ga-FAPI-04 and 18 F-FDG PET/CT within 1 week, including 30 patients who underwent simultaneous abdominal 68 Ga-FAPI-04 PET/MR scanning. The findings were confirmed by histopathology or radiographic follow-up. RESULTS: Compared with 18 F-FDG PET/CT, 68 Ga-FAPI-04 PET/CT showed higher sensitivity (94.3% vs 88.6%) and the same accuracy (86.4% vs 86.4%) in evaluating primary tumors. However, its specificity was lower (55.6% vs 77.8%). 68 Ga-FAPI-04 PET was superior to 18 F-FDG PET in both patient-based and lesion-based evaluations except for metastatic lesions in the liver and bone. For intrahepatic CCA, 68 Ga-FAPI-04 PET/CT and 18 F-FDG PET/CT (100% vs 100%) had similar detection rates, with similar uptake levels between tracers ( P > 0.05). However, for extrahepatic CCA, 68 Ga-FAPI-04 PET/CT had a higher detection rate (89.5% vs 78.9%), and 68 Ga-FAPI-04 had a higher uptake ( P < 0.05). PET/MR was more effective than PET/CT in terms of lesion conspicuity and diagnostic confidence for primary tumors and liver metastases. In addition, multisequence MRI identified more liver metastases than 68 Ga-FAPI-04 PET/CT and 18 F-FDG PET/CT. CONCLUSIONS: Compared with 18 F-FDG PET/CT, 68 Ga-FAPI-04 PET/CT showed a higher sensitivity in detecting primary CCA tumors, involved lymph nodes, and peritoneal metastases. Compared with 68 Ga-FAPI-04 PET/CT, PET/MR detected primary and liver metastatic lesions more accurately. For extrahepatic CCA, the combination of 68 Ga-FAPI-04 PET/CT and abdominal PET/MRI may replace 18 F-FDG PET/CT.

Simulating the impact of optimized prevention and control measures on the transmission of monkeypox in the United States: A model-based study.

This study aimed to develop a modified susceptible-exposed-infected-recovered (SEIR) model to evaluate monkeypox epidemics in the United States and explore more optimized prevention and control measures. To further assess the impact of public health measures on the transmission of monkeypox, different intervention scenarios were developed based on the classic SEIR model, considering reducing contact, enhancing vaccination, diagnosis delay, and environmental transmission risk, respectively. We evaluated the impact of different measures by simulating their spread in different scenarios. During the simulation period, 8709 people were infected with monkeypox. The simulation analysis showed that: (1) the most effective measures to control monkeypox transmission during the early stage of the epidemic were reducing contact and enhancing vaccination, with cumulative infections at 51.20% and 41.90% of baseline levels, respectively; (2) shortening diagnosis time would delay the peak time of the epidemic by 96 days; and (3) the risk of environmental transmission of monkeypox virus was relatively low. This study indirectly proved the effectiveness of the prevention and control measures, such as reducing contact, enhancing vaccination, shortening diagnosis time, and low risk of environmental transmission, which also provided an important reference and containment experience for nonepidemic countries.

Elevated 68 Ga-FAPI-04 Activity Due to Staphylococcus aureus Intracranial Infection.

ABSTRACT: A 37-year-old man was admitted to our hospital after experiencing syncope. An MRI of his head revealed multiple foci of abnormal signal, which could potentially be metastases. The patient then underwent a 68 Ga-FAPI-04 PET/MRI examination, which revealed multiple FAPI-avid foci in the brain. Upon analyzing the cerebrospinal fluid, it was found that the patient had a Staphylococcus aureus infection. The results suggest that 68 Ga-FAPI-04 PET has the potential to be a valuable tool in the visualization of intracranial infectious lesions.

Meteorological factors cannot be ignored in machine learning-based methods for predicting dengue, a systematic review.

In recent years, there has been a rapid increase in the application of machine learning methods about predicting the incidence of dengue fever. However, the predictive factors and models employed in different studies vary greatly. Hence, we conducted a systematic review to summarize machine learning methods and predictors in previous studies. We searched PubMed, ScienceDirect, and Web of Science databases for articles published up to July 2023. The selected papers included not only the forecast of dengue incidence but also machine learning methods. A total of 23 papers were included in this study. Predictive factors included meteorological factors (22, 95.7%), historical dengue data (14, 60.9%), environmental factors (4, 17.4%), socioeconomic factors (4, 17.4%), vector surveillance data (2, 8.7%), and internet search data (3, 13.0%). Among meteorological factors, temperature (20, 87.0%), rainfall (20, 87.0%), and relative humidity (14, 60.9%) were the most commonly used. We found that Support Vector Machine (SVM) (6, 26.1%), Long Short-Term Memory (LSTM) (5, 21.7%), Random Forest (RF) (4, 17.4%), Least Absolute Shrinkage and Selection Operator (LASSO) (2, 8.7%), ensemble model (2, 8.7%), and other models (4, 17.4%) were identified as the best models based on evaluation metrics used in each article. These results indicate that meteorological factors are important predictors that cannot be ignored and SVM and LSTM algorithms are the most commonly used models in dengue fever prediction with good predictive performance. This review will contribute to the development of more robust early dengue warning systems and promote the application of machine learning methods in predicting climate-related infectious diseases.

Association between behavioral patterns and depression symptoms: dyadic interaction between couples.

Background: Behavioral patterns are sometimes associated with depression symptoms; however, few studies have considered the intra-couple effects. This study examined the effect of a spouses' behavioral patterns on depression symptoms within themself and in their spouse. Methods: A total of 61,118 childbearing age participants (30,559 husband-wife dyads) were surveyed. The depression symptoms were assessed using the nine-item Patient Health Questionnaire (PHQ-9). The behavioral patterns were identified by the latent class analysis. The effects of behavioral patterns on the couple's own depression symptoms (actor effect) and their partner's depression symptoms (partner effect) were analyzed using the Actor-Partner Interdependence Model (APIM). Results: Three behavioral patterns were identified: low-risk group, moderate-risk group, and high-risk group. The high risk of these behavior patterns would be associated with a higher score on the PHQ-9; for both husbands and wives, their behavioral patterns were positively associated with PHQ-9 scores (ßhusband = 0.53, P < 0.01; ßwife = 0.58, P < 0.01). Wives' behavioral patterns were also positively associated with their husbands' PHQ-9 scores (ß = 0.14, P < 0.01), but husbands' behavioral patterns were not associated with their wives' PHQ-9 scores. Conclusions: Wives' depression symptoms were affected only by their own behavioral patterns, whereas husbands' depression symptoms were influenced by both their own and their spouses' behavioral patterns.

Associations of family income and healthy lifestyle with all-cause mortality.

Background: There is a lack of evidence on whether combined lifestyle factors mediate the association between family income and all-cause mortality, as well as the joint relations between family income and lifestyle factors with mortality. Methods: Using data on family income and lifestyle factors of participants in the US National Health Interview Survey 2016-2018, we performed multivariable logistic regression models to estimate the odds ratios (ORs) and 95% confidence intervals (CI) for the association of all-cause mortality with said data. Results: We included 73 729 participants with a mean age of 47.1 years (standard deviation (SD) = 18.0), 51% of whom were women and 65% of whom were non-Hispanic Whites. There were 2284 deaths documented. After multivariable adjustment, middle-income participants had an OR of 0.73 (95% CI = 0.61-0.88) for mortality, while high-income participants had an OR of 0.47 (95% CI = 0.37-0.60) compared with low-income participants. We found that lower all-cause mortality was related to higher lifestyle scores. Adults from high-income families with lifestyle scores of 3 and 4 had an OR for mortality of 0.44 (95% CI = 0.30-0.65) compared to those from low-income families and lifestyle scores of 0 or 1. When comparing those in highest vs lowest income groups in the mediation analysis, 9.8% (95% CI = 7.4-13.0) of the relation for all-cause mortality was mediated by lifestyles. Adults from high-income families with lifestyle scores of 3 or 4 had an OR of 0.23 (95% CI = 0.17-0.33) for mortality compared with those from low-income families and lifestyle scores of 0 or 1. Conclusions: A lower risk of all-cause mortality was linked to higher family income and healthier lifestyles. Furthermore, lifestyle factors mediated a small proportion of the association between family income and mortality among US adults. Economic disparity in health may not be eliminated by changing only one's lifestyle. Therefore, besides promoting a healthy lifestyle, we should stress how family income inequality affects health outcomes.

Traffic-related air pollution, adherence to healthy lifestyles, and risk of cognitive impairment: A nationwide population-based study.

BACKGROUND: Traffic-related air pollution (TRAP) is a risk factor for cognitive function, whereas healthy lifestyles are associated with better cognition. We aimed to examine their joint effects on cognition among the Chinese elderly. METHODS: The data from the Chinese Longitudinal Healthy Longevity Survey was used. Participants' cognitive performance was assessed by the Chinese version of the mini-mental state examination. Residential proximity to major roadways was obtained through self-report and categorized into five categories: > 300 m, 201-300 m, 101-200 m, 50-100 m, and < 50 m, serving as a surrogate for TRAP. Six lifestyle behaviors (smoking, drinking, exercise, body mass index, sleep duration, and dietary diversity) were taken into account to calculate healthy lifestyle scores. The scores ranged from zero to six and were then divided into three groups: healthy (5-6), intermediate (2-4), and unhealthy (0-1). Logistic regression models were applied to investigate the joint effects of TRAP and healthy lifestyle scores on cognition. RESULTS: Compared to participants living < 50 m from major roadways and adopting an unhealthy lifestyle, those living > 300 m from major roadways and adopting a healthy lifestyle had a significantly decreased risk of cognitive impairment. Stratified analysis indicated that the associations between TRAP and cognitive impairment were more pronounced among participants adopting an unhealthy lifestyle compared to the participants adopting a healthy lifestyle. CONCLUSIONS: TRAP may impair cognitive function, and its detrimental impacts may be lessened by healthy lifestyles.

Incremental value of 99m Tc-MIBI single-photon emission computed tomography/computed tomography fusion imaging for the diagnosis of secondary hyperparathyroidism.

PURPOSE: To assess the added value of 99m Tc-MIBI single-photon emission computed tomography/computed tomography (SPECT/CT) fusion imaging over dual-phase scintigraphy in the diagnosis of secondary hyperparathyroidism (SHPT). METHODS: This retrospective study included 23 patients with SHPT. The diagnostic efficacy of 99m Tc-MIBI dual-phase scintigraphy and SPECT/CT fusion imaging was analyzed and compared based on the result of postoperative pathology and follow-up. To evaluate the diagnostic ability of 99m Tc-MIBI dual-phase scintigraphy, the volume and radioactive count of parathyroid lesions were assessed using the region of interest method. RESULTS: A total of 79 hyperplastic parathyroid glands and two thyroid tissues were surgically removed from 23 SHPT patients and 13 normal parathyroid glands were preserved. 99m Tc-MIBI SPECT/CT fusion imaging showed higher sensitivity and accuracy than 99m Tc-MIBI dual-phase scintigraphy [sensitivity, 77.2% (61/79) vs 46.8% (37/79); accuracy, 80.4% (74/92) vs 54.3% (50/92), respectively], but comparable specificity [100% (13/13)). Among 61 positive lesions detected by 99m Tc-MIBI SPECT/CT fusion imaging, 37 were dual-phase scintigraphy positive and 24 were dual-phase scintigraphy false negative. The radioactivity counts and radioactivity per unit volume in dual-phase scintigraphy positive were higher than that in dual-phase scintigraphy false negative ( P  < 0.05), but the volume of parathyroid lesions between the two groups had no significant difference ( P  > 0.05). CONCLUSION: Compared with 99m Tc-MIBI dual-phase scintigraphy, 99m Tc-MIBI SPECT/CT fusion imaging has incremental value in the diagnosis of SHPT. The low uptake of MIBI in the whole gland and low MIBI uptake per unit volume are easy to cause dual-phase scintigraphy false negative.

Global Chronic obstructive pulmonary disease burden attributable to air pollution from 1990 to 2019.

BACKGROUND: The disease burden attributable to chronic obstructive pulmonary disease (COPD) is significant worldwide. Some studies have linked exposure to air pollution to COPD, but there has been little research on this. METHODS: We aimed to assess the COPD-related disease burden attributable to air pollution from multiple epidemiological perspectives. This study conducted a three-stage analysis. Firstly, we reported on the burden of disease worldwide in 2019 by different subgroups including sex, age, region, and country. Secondly, we studied the trends in disease burden from 1990 to 2019. Finally, we explored the association of some national indicators with disease burden to look for risk factors. RESULTS: In 2019, the death number of COPD associated with air pollution accounted for 2.32% of the total global death, and the number of DALY accounted for 1.12% of the global DALY. From 1990 to 2019, the death number of COPD associated with air pollution increased peaked at 1.41 million in 1993, fluctuated, and then declined. We found the same temporal pattern of DALY. The corresponding age-standardized rates had been falling. At the same time, the burden of COPD associated with air pollution was also affected by some national indicators. CONCLUSIONS: This study indicated that air pollution-related COPD contributed to a significant global disease burden. We called for health policymakers to take action and interventions targeting vulnerable countries and susceptible populations.

Interaction between home and community-based services and PM2.5 on cognition: A prospective cohort study of Chinese elderly.

PM2.5 and home and community-based services (HCBSs) had been shown to affect cognition, but the evidence on their joint effects was limited. Aimed to study the joint effects of HCBSs and PM2.5 on cognition, we utilized the follow-up data of participants in the Chinese Longitudinal Health Longevity Survey (CLHLS) who were 65 years of age or older and had normal cognitive function at baseline for the 2008-2018, 2011-2018, and 2014-2018 waves. 16,954, 9,765, and 7192 participants from each of these three waves were initially recruited, respectively. The PM2.5 concentration data of each province in China from 2008 to 2018 was obtained from the Atmospheric Composition Analysis Group. Participants were asked what kind of HCBSs were available in their community. The cognitive status of the participants was evaluated by the Chinese version of Mini-Mental State Examination (CMMSE). We applied the Cox proportional hazard regression model to investigate the joint effects of HCBSs and PM2.5 on cognition and further stratified the analysis according to HCBSs. Hazard ratio (HR) and 95% confidence interval (95% CI) were calculated based on Cox models. During a median follow-up period of 5.2 years, 911 (8.8%) participants with normal baseline cognitive function developed cognitive impairment. Compared to participants without HCBSs and exposed to the highest level of PM2.5, those with HCBSs and exposed to the lowest level of PM2.5 had a significantly reduced risk of developing cognitive impairment (HR = 0.428, 95% CI: 0.303-0.605). The results from the stratified analysis revealed that the detrimental effect of PM2.5 on cognition was more pronounced in participants without HCBSs (HR = 3.44, 95% CI: 2.18-5.41) compared with those with HCBSs (HR = 1.42, 95% CI: 0.77-2.61). HCBSs may attenuate the harmful impact of PM2.5 on cognitive status in the elderly Chinese and the government should further promote the application of HCBSs.

Interaction between the animal-based dietary pattern and green space on cognitive function among Chinese older adults: A prospective cohort study.

Green space is associated with better cognition, while the animal-based dietary pattern can be a risk factor. We aimed to verify the associations and explore their interaction among the elderly. The China Longitudinal Healthy Longevity Survey (CLHLS) cohort including 17,827 participants was used. The average green space coverage rate was used to measure green space exposure. The animal-based diet index (ADI) was scored based on the non-quantitative frequency questionnaire of ten types of food intake (three types of animal foods and seven types of plant foods). We used the Mini-Mental State Examination (MMSE) to assess cognitive function. The Cox proportional hazard regression was applied to explore the correlations and interactions. In the models, we gradually adjusted for the potential risk factors. Compared with participants living in the area with the lowest green space, those living with the highest were associated with a 20% decrease in the risk of cognitive impairment (hazard ratio (HR): 0.80, 95% CI: 0.73, 0.89). As for ADI, the highest group was related to a 64% increase in the risk of cognitive impairment (HR: 1.64, 95% CI: 1.38, 1.95). The protective effect of the highest green space group on cognitive impairment was more evident among participants with low ADI (HR = 0.72, 95% CI: 0.62, 0.83), compared to those with high ADI. Green space was positively associated with cognition, while the animal-based dietary pattern was a cognitive disadvantage. The animal-based dietary pattern may mitigate the beneficial effects of green space on cognition.

The combined effect of heavy metals and polycyclic aromatic hydrocarbons on arthritis, especially osteoarthritis, in the U.S. adult population.

The evaluation of heavy metals (HMs) and polycyclic aromatic hydrocarbons (PAHs) impact on arthritis is usually limited to the analysis of the arthritis subtype (rheumatoid arthritis, RA), whereas studies on osteoarthritis (OA) are relatively sparse. Furthermore, the combined effect of HMs and PAHs co-exposure on arthritis also has rarely been analyzed. Herein, we aimed to comprehensively estimate the association between HMs and PAHs (three blood HMs and six urinary PAHs metabolites) co-exposure and arthritis. Using data from the National Health and Nutrition Examination Survey (NHANES), 2003-2016, we included 9735 adults, of whom 2464 had total arthritis, 1371 had OA, and 468 had RA. The logistic regression model was conducted to estimate the single effect of HMs and PAHs on arthritis. Moreover, weighted quantile sum (WQS) regression, quantile-based g computation (qgcomp), and Bayesian kernel machine regression (BKMR) were separately performed to assess the combined effect of HMs and PAHs co-exposure on arthritis. In the single-exposure analyses, cadmium (Cd) and lead (Pb) statistically grew the risk of total arthritis, OA, and RA. Among PAHs, 1-hydroxynaphthalene (1-NAP) and 3-hydroxyfluorene (3-FLU) showed a positive association with total arthritis, OA, and RA. Meanwhile, 2-NAP also was significantly associated with total arthritis. 2-NAP, 2-FLU, and 1-hydroxyphenanthrene (1-PHE) also were significantly associated with RA. Furthermore, the three complementary models consistently demonstrated that co-exposure to high levels of HMs and PAHs was positively associated with total arthritis, OA, and RA risk. The above associations were more obvious in young and medium-aged people. Interestingly, BKMR analyses indicated that 1-NAP might interact with Cd and 3-FLU in total arthritis, while Pb might interact with Cd in OA. Therefore, this study provided novel evidence that co-exposure to HMs and PAHs positively correlated with arthritis, especially OA, and these results were worthy of further prospective studies.

Association between antibiotic exposure and the risk of infertility in women of childbearing age: A case-control study.

BACKGROUND: Based on self-report questionnaires, two previous epidemiological studies investigated the association between the exposure of women to antibiotics and their fertility. However, biomonitoring studies on low-dose antibiotic exposure, mainly from food and water, and its relation to the risk of infertility are missing. METHODS: Based on a case-control study design, 302 women with infertility (144 primary infertility, 158 secondary infertility) and 302 women with normal fertility, all aged 20-49 years, were recruited from Anhui Province, China, in 2020 and 2021. A total of 41 common antibiotics and two antibiotic metabolites in urine samples were determined by liquid chromatography-triple quadrupole tandem mass spectrometry (LC-QqQ-MS/MS). RESULTS: Twenty-eight antibiotics with detection rates from 10% to 100% in both cases (median concentration: ∼2.294 ng/mL) and controls (∼1.596 ng/mL) were included in the analysis. Logistic regression analysis revealed that after controlling for confounding factors, high concentrations of eight individual antibiotics (sulfamethoxazole, sulfaclozine, sulfamonomethoxine, penicillin G, chlorotetracycline, ofloxacin, norfloxacin, and cyadox) and four antibiotic classes (sulfonamides, tetracyclines, quinoxalines, and veterinary antibiotics) were related to a high risk of female infertility, with odds ratios (ORs) ranging from 1.30 to 2.86, except for chlorotetracycline (OR = 6.34), while another nine individual antibiotics (sulfamethazine, azithromycin, cefaclor, amoxicillin, oxytetracycline, pefloxacin, sarafloxacin, enrofloxacin, and florfenicol) and classes of chloramphenicol analogs and human antibiotics were related to a reduced risk of infertility, with ORs ranging from 0.70 to 0.20. Based on restricted cubic spline models after controlling for confounding factors, we observed that the relationship between all of the above protective antibiotics and infertility was nonlinear: A certain concentration could reduce the risk of female infertility while exceeding a safe dose could increase the risk of infertility. CONCLUSION: These results provide preliminary evidence that the effects of antibiotics on female fertility vary based on the active ingredient and usage and imply the importance of exposure dose. Future studies are needed to verify these results by controlling for multiple confounding factors.

Changing trends in the air pollution-related disease burden from 1990 to 2019 and its predicted level in 25 years.

In the twenty-first century, exposure to air pollution has become a threat to human health worldwide due to industrial development. Timely, comprehensive, and reliable assessment and prediction of disease burden can help mitigate the health hazards of air pollution. This study conducted a two-stage analysis. First, we reported the air pollution-related disease burden globally and for different subgroups like socio-demographic index (SDI), sex, and age. We analyzed the trend of the disease burden from 1990 to 2019. In addition, we explored whether and how some national indicators modified the disease burden. Second, we predicted the number and the age-standardized rates of death and disability-adjusted life years (DALYs) attributable to air pollution from 2020 to 2044 by the autoregressive integrated moving average (ARIMA) model and exponential smoothing model. The age-period-cohort (APC) model in the maximum likelihood framework and the Bayesian APC model integrated nested Laplace approximations (INLAs) were further applied to perform sensitivity analysis. In 2019, air pollution accounted for 11.62% of death and 0.84% of DALY worldwide. The corresponding age-standardized rate was 85.62 (95% uncertainty interval (UI): 75.71, 96.07) and 2791.08 (95% UI: 2468.81, 3141.39) per 100,000 population. From 1990 to 2019, the number of death attributable to air pollution remained stable, and the number of DALY exhibited a downward trend. The corresponding age-standardized rates both declined. In some countries with larger population densities, higher proportions of elders, and lower proportions of females, the disease burden attributable to air pollution was lower. The predicted results showed that the number of air pollution-related death and DALY would increase. This study comprehensively assessed and predicted the air pollution-related disease burden worldwide. The results indicated that the disease burden would remain very serious in the future. Hence, some relevant policies should be developed to prevent and manage air pollution.

Molecular imaging of fibroblast activity in pressure overload heart failure using [68 Ga]Ga-FAPI-04 PET/CT.

PURPOSE: We aimed to evaluate whether [68 Ga]Ga-FAPI-04 PET/CT could characterize the early stages of cardiac fibrosis in pressure overload heart failure. METHODS: Sprague-Dawley rats underwent abdominal aortic constriction (AAC) (n = 12) and sham surgery (n = 10). All rats were scanned with [68 Ga]Ga-FAPI-04 PET/CT at 2, 4, and 8 weeks after surgery. The expression of fibroblast activation protein (FAP) in the myocardium was detected by immunohistochemistry. [68 Ga]Ga-FAPI-04 PET signal and FAP expression were compared between two groups. RESULTS: Compared with the sham group, the AAC group presented with decreased ejection fraction (EF) and fractional shortening (FS) and increased left ventricular internal dimensions in diastole (LVIDd) and systole (LVIDs) at 4 and 8 weeks (all p < 0.01). The AAC group showed higher [68 Ga]Ga-FAPI-04 accumulation in the heart than the sham group at 2, 4, and 8 weeks, and FAPI increased significantly from 2 to 8 weeks (all p < 0.001). Immunohistochemistry confirmed the higher density of the FAP+ area in the AAC group. The intensity of the [68 Ga]Ga-FAPI-04 correlated with the density of the FAP+ area (p < 0.001). The expression of the [68 Ga]Ga-FAPI-04 at 4 weeks correlated with the deterioration of cardiac function at 8 weeks (EF: R = - 0.87; FS: R = - 0.72; LVIDd: R = 0.77; LVIDs: R = 0.79; all p < 0.001). The AAC group also showed an increased [68 Ga]Ga-FAPI-04 signal in the liver, peaking at 4 weeks and then declining. Cardiac and liver PET signals correlated at 4 weeks in the AAC group (R = 0.69, p = 0.0010), suggesting an early fibrotic link between organs. A combination of the [68 Ga]Ga-FAPI-04 intensity in the heart and liver at 4 weeks better predicted the deterioration of cardiac function at 8 weeks. CONCLUSIONS: The activated fibroblasts in the heart and liver after pressure overload can be monitored by [68 Ga]Ga-FAPI-04 PET/CT, which reveals an early fibrotic link in cardio-liver interactions and could better predict nonischemic heart failure prognosis.

Changing trends in the disease burden of non-melanoma skin cancer globally from 1990 to 2019 and its predicted level in 25 years.

BACKGROUND: The disease burden of non-melanoma skin cancer (NMSC) has become a significant public health threat. We aimed to conduct a comprehensive analysis to mitigate the health hazards of NMSC. METHODS: This study had three objectives. First, we reported the NMSC-related disease burden globally and for different subgroups (sex, socio-demographic index (SDI), etiology, and countries) in 2019. Second, we examined the temporal trend of the disease burden from 1990 to 2019. Finally, we used the Bayesian age-period-cohort (BAPC) model integrated nested Laplacian approximation to predict the disease burden in the coming 25 years. The Norpred age-period-cohort (APC) model and the Autoregressive Integrated Moving Average (ARIMA) model were used for sensitivity analysis. RESULTS: The disease burden was significantly higher in males than in females in 2019. The results showed significant differences in disease burden in different SDI regions. The better the socio-economic development, the heavier the disease burden of NMSC. The number of new cases and the ASIR of basal cell carcinoma (BCC) were higher than that of squamous cell carcinoma (SCC) in 2019 globally. However, the number of DALYs and the age-standardized DALYs rate were the opposite. There were statistically significant differences among different countries. The age-standardized incidence rate (ASIR) of NMSC increased from 54.08/100,000 (95% uncertainty interval (UI): 46.97, 62.08) in 1990 to 79.10/100,000 (95% UI: 72.29, 86.63) in 2019, with an estimated annual percentage change (EAPC) of 1.78. Other indicators (the number of new cases, the number of deaths, the number of disability-adjusted life years (DALYs), the age-standardized mortality rate (ASMR), and the age-standardized DALYs rate) showed the same trend. Our predictions suggested that the number of new cases, deaths, and DALYs attributable to NMSC would increase by at least 1.5 times from 2020 to 2044. CONCLUSIONS: The disease burden attributable to NMSC will continue to increase or remain stable at high levels. Therefore, relevant policies should be developed to manage NMSC, and measures should be taken to target risk factors and high-risk groups.

Molecular imaging on ACE2-dependent transocular infection of coronavirus.

A transocular infection has been proved as one of the main approaches that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invades the body, and angiotensin-converting enzyme 2 (ACE2) plays a key role in this procedure. Dynamic and quantitative details on virus distribution are lacking for virus prevention and drug design. In this study, a radiotraceable pseudovirus packed with an enhanced green fluorescent protein (EGFP) gene, 125 I-CoV, was prepared and inoculated in the unilateral eye of humanized ACE2 (hACE2) mice or ACE2-knockout (ACE2-KO) mice. Single-photon emission computed tomography/computed tomography images were acquired at multiple time points to exhibit ACE2-dependent procedures from invasion to clearance. Positron emission tomography (PET) and western blot were performed to quantify ACE2 expression and verify the factors affecting transocular infection. For the transocular infection of coronavirus (CoV), the renin-angiotensin-aldosterone system (RAAS), lungs, intestines, and genital glands were the main targeted organs. Due to the specific anchor to ACE2-expressed host cells, virus concentrations in genital glands, liver, and lungs ranked the top three most and stabilized at 3.75 ± 0.55, 3.30 ± 0.25, and 2.10 ± 0.55% inoculated dose (ID)/mL at 48 h post treatment. Meanwhile, ACE2-KO mice had already completed the in vivo clearance. In consideration of organ volumes, lungs (14.50 ± 3.75%ID) and liver (10.94 ± 0.71%ID) were the main in-store reservoirs of CoV. However, the inoculated eye (5.52 ± 1.85%ID for hACE2, 5.24 ± 1.45%ID for ACE2-KO, p > 0.05) and the adjacent brain exhibited ACE2-independent virus infection at the end of 72 h observation, and absolute amount of virus played a key role in host cell infection. These observations on CoV infection were further manifested by infection-driven intracellular EGFP expression. ACE2 PET revealed an infection-related systematic upregulation of ACE2 expression in the organs involved in RAAS (e.g., brain, lung, heart, liver, and kidney) and the organ that was of own local renin-angiotensin system (e.g., eye). Transocular infection of CoV is ACE2-dependent and constitutes the cause of disturbed ACE2 expression in the host. The brain, genital glands, and intestines were of the highest unit uptake, potentially accounting for the sequelae. Lungs and liver were of the highest absolute amount, closely related to the respiratory diffusion and in vivo duplication. ACE2 expression was upregulated in the short term after infection with CoV. These visual and quantitative results are helpful to fully understanding the transocular path of SARS-CoV-2 and other CoVs.

Comparison of the diagnostic efficacy of 68 Ga-FAPI-04 PET/MR and 18F-FDG PET/CT in patients with pancreatic cancer.

PURPOSE: We sought to assess the performance of 68 Ga-FAPI-04 PET/MR for the diagnosis of primary tumours as well as metastatic lesions in patients with pancreatic cancer and to compare the results with those of 18F-FDG PET/CT. METHODS: Prospectively, we evaluated 33 patients suspected to have pancreatic adenocarcinoma, of whom thirty-two were confirmed by histopathology, and one had autoimmune pancreatitis confirmed by needle biopsy and glucocorticoid treatment. Within 1 week, each patient underwent both 68 Ga-FAPI-04 PET/MR and 18F-FDG PET/CT. Comparisons of the detection abilities for primary tumours, lymph nodes, and metastases were conducted for the two imaging approaches. The original maximum standard uptake values (SUVmax) and normalised SUVmax (SUVmax/SUVbkgd) of paired lesions on 68 Ga-FAPI-04 PET/MR and 18F-FDG PET/CT were measured and compared. RESULTS: Thirty pancreatic cancer patients and three pancreatitis patients were enrolled. 68 Ga-FAPI-04 PET/MR and 18F-FDG PET/CT exhibited equivalent (100%) detection rates for primary tumours. The original/normalised SUVmax of primary tumours on 68 Ga-FAPI-04 PET was markedly higher than that on 18F-FDG (p < 0.05). Sixteen pancreatic cancer patients had pancreatic parenchymal uptake, whereas 18F-FDG PET images showed parenchymal uptake in only four patients (53.33% vs. 13.33%, p < 0.001). 68 Ga-FAPI-04 PET detected more positive lymph nodes than 18F-FDG PET (42 vs. 30, p < 0.001), while 18F-FDG PET was able to detect more liver metastases than 68 Ga-FAPI-04 (181 vs. 104, p < 0.001). In addition, multisequence MR imaging helped explain ten pancreatic cancers that could not be definitively revealed due to 68 Ga-FAPI-04 inflammatory uptake and identified more liver metastases than 18F-FDG (256 vs. 181, p < 0.001). CONCLUSION: 68 Ga-FAPI-04 PET might be better than 18F-FDG PET in the detection of suspicious lymph node metastases. MR multiple sequence imaging of 68 Ga-FAPI-04 PET/MR was helpful for explaining pancreatic lesions in patients with obstructive inflammation and detecting tiny liver metastases.

Retraction: ASIC1a involves acidic microenvironment-induced activation and autophagy of pancreatic stellate cells.

[This retracts the article DOI: 10.1039/C8RA03679A.].

Non-Causal Effects of Asthma on COVID-19 Susceptibility and Severity.

Background: Asthma is observationally associated with an increased risk of COVID-19, but the causality remains unclear. We aim to determine whether there is a casual role of asthma in susceptibility to SARS-CoV-2 infection or COVID-19 severity. Methods: Instrumental variables (IVs) for asthma and moderate-to-severe asthma were obtained from publicly available summary statistics from the most recent and largest genome-wide association study (GWAS), including 394 283 and 57 695 participants of European ancestry, respectively. The corresponding data for COVID-19 susceptibility, hospitalization and severe-disease were derived from the COVID-19 Host Genetics Initiative GWAS meta-analysis of up to 1 683 768 individuals of European descent. Causality was inferred between correlated traits by Mendelian Randomization analyses. Inverse-variance weighted method was used as the primary MR estimates and multiple alternate approaches and several sensitivity analyses were also conducted. Results: Our MR analysis revealed no causal effects of asthma on COVID-19 susceptibility, hospitalization or severe disease, with odds ratio (OR) of 0.994 (95% CI: 0.962-1.027), 1.020 (95% CI: 0.955-1.089), and 0.929 (95% CI: 0.836-1.032), respectively. Furthermore, using genetic variants for moderate-to-severe asthma, a similar pattern of results was observed for COVID-19 susceptibility (OR: 0.988, 95% CI: 0.946-1.031), hospitalization (OR: 0.967, 95% CI: 0.906-1.031), and severe disease (OR: 0.911, 95% CI: 0.823-1.009). The association of asthma and moderate-to-severe asthma with COVID-19 was overall robust to sensitivity analyses. Conclusion: Genetically predicted asthma was not associated with susceptibility to, or severity of, COVID-19 disease, indicating that asthma is unlikely to be a causal factor in the development of COVID-19.