Image-guided percutaneous ablation of hepatic epithelioid hemangioendothelioma.

PURPOSE: Disease control and survival following percutaneous ablation of hepatic epithelioid hemangioendothelioma (EHE) was studied retrospectively. METHODS: Six patients underwent 16 image-guided ablation procedures to treat 35 liver tumors from 2015 to 2022 (17 microwave ablation, 9 irreversible electroporation, 8 cryoablation, and 1 radiofrequency ablation). Technical success, local progression, intrahepatic progression, distant progression, overall survival, and adverse events were assessed. RESULTS: Four of six (67%) patients were treatment naïve prior to ablation. The mean length of imaging follow-up from first ablation procedure was 43.0 ± 31.2 months. Thirty-three of 35 (94.3%) ablated tumors did not progress locally. Three of 6 patients (50%) had new intrahepatic progression and underwent repeat ablation or systemic treatment. No extrahepatic progression was observed. One patient died from EHE 2.7 years after initial diagnosis. No severe adverse events occurred. CONCLUSION: Percutaneous ablation is feasible, often in a staged fashion, and may provide favorable intermediate to long-term disease control for patients with hepatic EHE.

Unraveling attributes of COVID-19 vaccine acceptance and uptake in the U.S.: a large nationwide study.

SARS-CoV-2 vaccines are useful tools to combat the Coronavirus Disease 2019 (COVID-19) pandemic, but vaccine reluctance threatens these vaccines' effectiveness. To address COVID-19 vaccine reluctance and ensure equitable distribution, understanding the extent of and factors associated with vaccine acceptance and uptake is critical. We report the results of a large nationwide study in the US conducted December 2020-May 2021 of 36,711 users from COVID-19-focused smartphone-based app How We Feel on their willingness to receive a COVID-19 vaccine. We identified sociodemographic and behavioral factors that were associated with COVID-19 vaccine acceptance and uptake, and we found several vulnerable groups at increased risk of COVID-19 burden, morbidity, and mortality were more likely to be reluctant to accept a vaccine and had lower rates of vaccination. Our findings highlight specific populations in which targeted efforts to develop education and outreach programs are needed to overcome poor vaccine acceptance and improve equitable access, diversity, and inclusion in the national response to COVID-19.

Image-Guided Ablation of Recurrent or Unresectable Intrahepatic Cholangiocarcinoma.

PURPOSE: To assess the safety and effectiveness of image-guided ablation of recurrent or unresectable intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: In this retrospective study, 25 patients (14 women; age, 36-84 years) underwent 37 image-guided liver tumor ablation procedures to treat 47 ICCs (May 2004 to January 2022). At initial diagnosis, 20 patients had Stage 1 or 2 disease and 5 had Stage 3 or 4 disease. Before ablation, 19 (76.0%) of the 25 patients had progressed through prior treatments, including resection (n = 11), chemotherapy (n = 11), transarterial embolization (n = 3), or radiotherapy (n = 1); 6 (24.0%) of the 25 patients were treatment naïve. Ablation modality selection was based on patient and tumor characteristics and operator preference. Primary outcomes included local progression-free survival (LPFS) and overall survival (OS) after ablation. Statistical analysis included Kaplan-Meier (KM) survival analyses and Cox proportional hazards models. RESULTS: The mean ablated tumor size was 2.0 cm ± 1.2 (range, 0.5-5.0 cm). The 1-, 2-, and 5-year LPFS rates were 84.0% (95% CI, 72.9-96.8), 73.0% (95% CI, 59.0-90.4), and 59.5% (95% CI, 41.6-85.1), respectively. The 1-, 2-, and 5-year secondary LPFS rates were 89.5% (95% CI, 80.2-99.9), 81.9% (95% CI, 69.4-96.6), and 75.6% (95% CI, 60.2-94.9). The 1-, 2-, and 5-year LPFS rates for tumors ≤2 cm in size were all 95.8% (95% CI, 88.2-100.0). The 1-, 2-, and 5-year OS rates were 78.5% (95% CI, 63.5-97.2), 68.4% (95% CI, 51.3-91.1), and 43.5% (95% CI, 23.5-80.5). Larger tumor size was associated with decreased time to local progression (hazard ratio, 1.93; P = .012). CONCLUSIONS: Percutaneous ablation provided favorable intermediate to long-term disease control for patients with recurrent or inoperable cholangiocarcinoma.

Differences in set-based tests for sparse alternatives when testing sets of outcomes compared to sets of explanatory factors in genetic association studies.

Set-based association tests are widely popular in genetic association settings for their ability to aggregate weak signals and reduce multiple testing burdens. In particular, a class of set-based tests including the Higher Criticism, Berk-Jones, and other statistics have recently been popularized for reaching a so-called detection boundary when signals are rare and weak. Such tests have been applied in two subtly different settings: (a) associating a genetic variant set with a single phenotype and (b) associating a single genetic variant with a phenotype set. A significant issue in practice is the choice of test, especially when deciding between innovated and generalized type methods for detection boundary tests. Conflicting guidance is present in the literature. This work describes how correlation structures generate marked differences in relative operating characteristics for settings (a) and (b). The implications for study design are significant. We also develop novel power bounds that facilitate the aforementioned calculations and allow for analysis of individual testing settings. In more concrete terms, our investigation is motivated by translational expression quantitative trait loci (eQTL) studies in lung cancer. These studies involve both testing for groups of variants associated with a single gene expression (multiple explanatory factors) and testing whether a single variant is associated with a group of gene expressions (multiple outcomes). Results are supported by a collection of simulation studies and illustrated through lung cancer eQTL examples.

COVID-19 Spread Mapper: a multi-resolution, unified framework and open-source tool.

SUMMARY: Amidst the continuing spread of coronavirus disease-19 (COVID-19), real-time data analysis and visualization remain critical the general public to track the pandemic's impact and to inform policy making by officials. Multiple metrics permit the evaluation of the spread, infection and mortality of infectious diseases. For example, numbers of new cases and deaths provide easily interpretable measures of absolute impact within a given population and time frame, while the effective reproduction rate provides an epidemiological measure of the rate of spread. By evaluating multiple metrics concurrently, users can leverage complementary insights into the impact and current state of the pandemic when formulating prevention and safety plans for oneself and others. We describe COVID-19 Spread Mapper, a unified framework for estimating and quantifying the uncertainty in the smoothed daily effective reproduction number, case rate and death rate in a region using log-linear models. We apply this framework to characterize COVID-19 impact at multiple geographic resolutions, including by US county and state as well as by country, demonstrating the variation across resolutions and the need for harmonized efforts to control the pandemic. We provide an open-source online dashboard for real-time analysis and visualization of multiple key metrics, which are critical to evaluate the impact of COVID-19 and make informed policy decisions. AVAILABILITY AND IMPLEMENTATION: Our model and tool are publicly available as implemented in R and hosted at https://metrics.covid19-analysis.org/. The source code is freely available from https://github.com/lin-lab/COVID19-Rt and https://github.com/lin-lab/COVID19-Viz. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Unraveling Attributes of COVID-19 Vaccine Hesitancy and Uptake in the U.S.: A Large Nationwide Study.

SARS-CoV-2 vaccines are powerful tools to combat the COVID-19 pandemic, but vaccine hesitancy threatens these vaccines’ effectiveness. To address COVID-19 vaccine hesitancy and ensure equitable distribution, understanding the extent of and factors associated with vaccine acceptance and uptake is critical. We report the results of a large nationwide study conducted December 2020-May 2021 of 34,470 users from COVID-19-focused smartphone-based app How We Feel on their willingness to receive a COVID-19 vaccine. Nineteen percent of respondents expressed vaccine hesitancy, the majority being undecided. Of those who were undecided or unlikely to get a COVID-19 vaccine, 86% reported they ultimately did receive a COVID-19 vaccine. We identified sociodemographic and behavioral factors that were associated with COVID-19 vaccine hesitancy and uptake, and we found several vulnerable groups at increased risk of COVID-19 burden, morbidity, and mortality were more likely to be vaccine hesitant and had lower rates of vaccination. Our findings highlight specific populations in which targeted efforts to develop education and outreach programs are needed to overcome vaccine hesitancy and improve equitable access, diversity, and inclusion in the national response to COVID-19.

Population-scale longitudinal mapping of COVID-19 symptoms, behaviour and testing.

Despite the widespread implementation of public health measures, coronavirus disease 2019 (COVID-19) continues to spread in the United States. To facilitate an agile response to the pandemic, we developed How We Feel, a web and mobile application that collects longitudinal self-reported survey responses on health, behaviour and demographics. Here, we report results from over 500,000 users in the United States from 2 April 2020 to 12 May 2020. We show that self-reported surveys can be used to build predictive models to identify likely COVID-19-positive individuals. We find evidence among our users for asymptomatic or presymptomatic presentation; show a variety of exposure, occupational and demographic risk factors for COVID-19 beyond symptoms; reveal factors for which users have been SARS-CoV-2 PCR tested; and highlight the temporal dynamics of symptoms and self-isolation behaviour. These results highlight the utility of collecting a diverse set of symptomatic, demographic, exposure and behavioural self-reported data to fight the COVID-19 pandemic.

Population-scale Longitudinal Mapping of COVID-19 Symptoms, Behavior, and Testing Identifies Contributors to Continued Disease Spread in the United States.

Despite social distancing and shelter-in-place policies, COVID-19 continues to spread in the United States. A lack of timely information about factors influencing COVID-19 spread and testing has hampered agile responses to the pandemic. We developed How We Feel, an extensible web and mobile application that aggregates self-reported survey responses, to fill gaps in the collection of COVID-19-related data. How We Feel collects longitudinal and geographically localized information on users' health, behavior, and demographics. Here we report results from over 500,000 users in the United States from April 2, 2020 to May 12, 2020. We show that self- reported surveys can be used to build predictive models of COVID-19 test results, which may aid in identification of likely COVID-19 positive individuals. We find evidence among our users for asymptomatic or presymptomatic presentation, as well as for household and community exposure, occupation, and demographics being strong risk factors for COVID-19. We further reveal factors for which users have been SARS-CoV-2 PCR tested, as well as the temporal dynamics of self- reported symptoms and self-isolation behavior in positive and negative users. These results highlight the utility of collecting a diverse set of symptomatic, demographic, and behavioral self- reported data to fight the COVID-19 pandemic.

Fluoride Depletes Acidogenic Taxa in Oral but Not Gut Microbial Communities in Mice.

Fluoridation of drinking water and dental products prevents dental caries primarily by inhibiting energy harvest in oral cariogenic bacteria (such as Streptococcus mutans and Streptococcus sanguinis), thus leading to their depletion. However, the extent to which oral and gut microbial communities are affected by host fluoride exposure has been underexplored. In this study, we modeled human fluoride exposures to municipal water and dental products by treating mice with low or high levels of fluoride over a 12-week period. We then used 16S rRNA gene amplicon and shotgun metagenomic sequencing to assess fluoride's effects on oral and gut microbiome composition and function. In both the low- and high-fluoride groups, several operational taxonomic units (OTUs) belonging to acidogenic bacterial genera (such as Parabacteroides, Bacteroides, and Bilophila) were depleted in the oral community. In addition, fluoride-associated changes in oral community composition resulted in depletion of gene families involved in central carbon metabolism and energy harvest (2-oxoglutarate ferredoxin oxidoreductase, succinate dehydrogenase, and the glyoxylate cycle). In contrast, fluoride treatment did not induce a significant shift in gut microbial community composition or function in our mouse model, possibly due to absorption in the upper gastrointestinal tract. Fluoride-associated perturbations thus appeared to have a selective effect on the composition of the oral but not gut microbial community in mice. Future studies will be necessary to understand possible implications of fluoride exposure for the human microbiome. IMPORTANCE Fluoride has been added to drinking water and dental products since the 1950s. The beneficial effects of fluoride on oral health are due to its ability to inhibit the growth of bacteria that cause dental caries. Despite widespread human consumption of fluoride, there have been only two studies of humans that considered the effect of fluoride on human-associated microbial communities, which are increasingly understood to play important roles in health and disease. Notably, neither of these studies included a true cross-sectional control lacking fluoride exposure, as study subjects continued baseline fluoride treatment in their daily dental hygiene routines. To our knowledge, this work (in mice) is the first controlled study to assess the independent effects of fluoride exposure on the oral and gut microbial communities. Investigating how fluoride interacts with host-associated microbial communities in this controlled setting represents an effort toward understanding how common environmental exposures may potentially influence health.

Solution and solid-state studies of 3,4-dichloro-2,5-diamidopyrroles: formation of an unusual anionic narcissistic dimer.

3,4-Dichoro-1H-pyrrole-2,5-dicarboxylic acid bis-phenylamide 3 and 3,4-dichoro-1H-pyrrole-2,5-dicarboxylic acid bis-butylamide 4 have been prepared and shown to deprotonate in the presence of basic anions: the X-ray crystal structure of the tetrabutylammonium salt of 3-H+ reveals the formation of a dimer in the solid state.