Immune escape and attenuated severity associated with the SARS-CoV-2 BA.2.86/JN.1 lineage.

The SARS-CoV-2 BA.2.86 lineage, and its sublineage JN.1 in particular, achieved widespread transmission in the US during winter 2023-24. However, the increase in infections was not accompanied by increases in COVID-19 hospitalizations and mortality commensurate with prior waves. To understand shifts in COVID-19 epidemiology associated with JN.1 emergence, we compared characteristics and clinical outcomes of time-matched cases infected with BA.2.86- derived lineages (predominantly representing JN.1) versus co-circulating XBB-derived lineages in December, 2023 and January, 2024. Cases infected with BA.2.86-derived lineages received greater numbers of COVID-19 vaccine doses, including XBB.1.5-targeted and BA.4/BA.5-targeted boosters, in comparison to cases infected with XBB-derived lineages. Additionally, cases infected with BA.2.86-derived lineages experienced greater numbers of documented prior SARS-CoV-2 infections. These associations of BA.2.86-derived lineages with immune escape were confirmed when comparing cases diagnosed during periods when JN.1 was the predominant circulating lineage to cases diagnosed during November, 2023. Cases infected with BA.2.86-derived lineages, or during periods when JN.1 was the predominant circulating lineage, also experienced lower risk of progression to severe clinical outcomes requiring emergency department consultations or hospital admission. Sensitivity analyses suggested under-ascertainment of prior infections, even if differential between cases infected with BA.2.86-derived lineages and non-BA.2.86 lineages, could not explain this apparent attenuation of severity. Our findings implicate escape from immunity acquired from prior vaccination or infection in the emergence of the JN.1 lineage and suggest infections with this lineage are less likely to experience clinically-severe disease. Monitoring of immune escape and clinical severity in emerging SARS-CoV-2 variants remains a priority to inform responses.

Development and validation of the Michigan Chronic Disease Simulation Model (MICROSIM).

Strategies to prevent or delay Alzheimer's disease and related dementias (AD/ADRD) are urgently needed, and blood pressure (BP) management is a promising strategy. Yet the effects of different BP control strategies across the life course on AD/ADRD are unknown. Randomized trials may be infeasible due to prolonged follow-up and large sample sizes. Simulation analysis is a practical approach to estimating these effects using the best available existing data. However, existing simulation frameworks cannot estimate the effects of BP control on both dementia and cardiovascular disease. This manuscript describes the design principles, implementation details, and population-level validation of a novel population-health microsimulation framework, the MIchigan ChROnic Disease SIMulation (MICROSIM), for The Effect of Lower Blood Pressure over the Life Course on Late-life Cognition in Blacks, Hispanics, and Whites (BP-COG) study of the effect of BP levels over the life course on dementia and cardiovascular disease. MICROSIM is an agent-based Monte Carlo simulation designed using computer programming best practices. MICROSIM estimates annual vascular risk factor levels and transition probabilities in all-cause dementia, stroke, myocardial infarction, and mortality in a nationally representative sample of US adults 18+ using the National Health and Nutrition Examination Survey (NHANES). MICROSIM models changes in risk factors over time, cognition and dementia using changes from a pooled dataset of individual participant data from 6 US prospective cardiovascular cohort studies. Cardiovascular risks were estimated using a widely used risk model and BP treatment effects were derived from meta-analyses of randomized trials. MICROSIM is an extensible, open-source framework designed to estimate the population-level impact of different BP management strategies and reproduces US population-level estimates of BP and other vascular risk factors levels, their change over time, and incident all-cause dementia, stroke, myocardial infarction, and mortality.

Post-COVID conditions following COVID-19 vaccination: a retrospective matched cohort study of patients with SARS-CoV-2 infection.

COVID-19 vaccinations protect against severe illness and death, but associations with post-COVID conditions (PCC) are less clear. We aimed to evaluate the association between prior COVID-19 vaccination and new-onset PCC among individuals with SARS-CoV-2 infection across eight large healthcare systems in the United States. This retrospective matched cohort study used electronic health records (EHR) from patients with SARS-CoV-2 positive tests during March 2021-February 2022. Vaccinated and unvaccinated COVID-19 cases were matched on location, test date, severity of acute infection, age, and sex. Vaccination status was ascertained using EHR and integrated data on externally administered vaccines. Adjusted relative risks (RRs) were obtained from Poisson regression. PCC was defined as a new diagnosis in one of 13 PCC categories 30 days to 6 months following a positive SARS-CoV-2 test. The study included 161,531 vaccinated COVID-19 cases and 161,531 matched unvaccinated cases. Compared to unvaccinated cases, vaccinated cases had a similar or lower risk of all PCC categories except mental health disorders (RR: 1.06, 95% CI: 1.02-1.10). Vaccination was associated with ≥10% lower risk of sensory (RR: 0.90, 0.86-0.95), circulatory (RR: 0.88, 0.83-0.94), blood and hematologic (RR: 0.79, 0.71-0.89), skin and subcutaneous (RR: 0.69, 0.66-0.72), and non-specific COVID-19 related disorders (RR: 0.53, 0.51-0.56). In general, associations were stronger at younger ages but mostly persisted regardless of SARS-CoV-2 variant period, receipt of ≥3 vs. 1-2 vaccine doses, or time since vaccination. Pre-infection vaccination was associated with reduced risk of several PCC outcomes and hence may decrease the long-term consequences of COVID-19.

Effect of Population-Level Blood Pressure Treatment Strategies on Cardiovascular and Cognitive Outcomes.

BACKGROUND: The large and increasing number of adults living with dementia is a pressing societal priority, which may be partially mitigated through improved population-level blood pressure (BP) control. We explored how tighter population-level BP control affects the incidence of atherosclerotic cardiovascular disease (ASCVD) events and dementia. METHODS: Using an open-source ASCVD and dementia simulation analysis platform, the Michigan Chronic Disease Simulation Model, we evaluated how optimal implementation of 2 BP treatments based on the Eighth Joint National Committee recommendations and SPRINT (Systolic Blood Pressure Intervention Trial) protocol would influence population-level ASCVD events, global cognitive performance, and all-cause dementia. We simulated 3 populations (usual care, Eighth Joint National Committee based, SPRINT based) using nationally representative data to annually update risk factors and assign ASCVD events, global cognitive performance scores, and dementia, applying different BP treatments in each population. We tabulated total ASCVD events, global cognitive performance, all-cause dementia, optimal brain health, and years lived in each state per population. RESULTS: Optimal implementation of SPRINT-based BP treatment strategy, compared with usual care, reduced ASCVD events in the United States by ≈77 000 per year and produced 0.4 more years of stroke- or myocardial infarction-free survival when averaged across all Americans. Population-level gains in years lived free of ASCVD events were greater for SPRINT-based than Eighth Joint National Committee-based treatment. Survival and years spent with optimal brain health improved with optimal SPRINT-based BP treatment implementation versus usual care: the average patient with hypertension lived 0.19 additional years and 0.3 additional years in optimal brain health. SPRINT-based BP treatment increased the number of years lived without dementia (by an average of 0.13 years/person with hypertension), but increased the total number of individuals with dementia, mainly through more adults surviving to advanced ages. CONCLUSIONS: Tighter BP control likely benefits most individuals but is unlikely to reduce dementia prevalence and might even increase the number of older adults living with dementia.

Attitudes Toward COVID-19 Vaccines Among Pregnant and Recently Pregnant Individuals.

Importance: Pregnant people and infants are at high risk of severe COVID-19 outcomes. Understanding changes in attitudes toward COVID-19 vaccines among pregnant and recently pregnant people is important for public health messaging. Objective: To assess attitudinal trends regarding COVID-19 vaccines by (1) vaccination status and (2) race, ethnicity, and language among samples of pregnant and recently pregnant Vaccine Safety Datalink (VSD) members from 2021 to 2023. Design, Setting, and Participants: This cross-sectional surveye study included pregnant or recently pregnant members of the VSD, a collaboration of 13 health care systems and the US Centers for Disease Control and Prevention. Unvaccinated, non-Hispanic Black, and Spanish-speaking members were oversampled. Wave 1 took place from October 2021 to February 2022, and wave 2 took place from November 2022 to February 2023. Data were analyzed from May 2022 to September 2023. Exposures: Self-reported or electronic health record (EHR)-derived race, ethnicity, and preferred language. Main Outcomes and Measures: Self-reported vaccination status and attitudes toward monovalent (wave 1) or bivalent Omicron booster (wave 2) COVID-19 vaccines. Sample- and response-weighted analyses assessed attitudes by vaccination status and 3 race, ethnicity, and language groupings of interest. Results: There were 1227 respondents; all identified as female, the mean (SD) age was 31.7 (5.6) years, 356 (29.0%) identified as Black race, 555 (45.2%) identified as Hispanic ethnicity, and 445 (36.3%) preferred the Spanish language. Response rates were 43.5% for wave 1 (652 of 1500 individuals sampled) and 39.5% for wave 2 (575 of 1456 individuals sampled). Respondents were more likely than nonrespondents to be White, non-Hispanic, and vaccinated per EHR. Overall, 76.8% (95% CI, 71.5%-82.2%) reported 1 or more COVID-19 vaccinations; Spanish-speaking Hispanic respondents had the highest weighted proportion of respondents with 1 or more vaccination. Weighted estimates of somewhat or strongly agreeing that COVID-19 vaccines are safe decreased from wave 1 to 2 for respondents who reported 1 or more vaccinations (76% vs 50%; χ21 = 7.8; P < .001), non-Hispanic White respondents (72% vs 43%; χ21 = 5.4; P = .02), and Spanish-speaking Hispanic respondents (76% vs 53%; χ21 = 22.8; P = .002). Conclusions and Relevance: Decreasing confidence in COVID-19 vaccine safety in a large, diverse pregnant and recently pregnant insured population is a public health concern.

Influence of SPION Surface Coating on Magnetic Properties and Theranostic Profile.

This study aimed to develop multifunctional nanoplatforms for both cancer imaging and therapy using superparamagnetic iron oxide nanoparticles (SPIONs). Two distinct synthetic methods, reduction-precipitation (MR/P) and co-precipitation at controlled pH (MpH), were explored, including the assessment of the coating's influence, namely dextran and gold, on their magnetic properties. These SPIONs were further functionalized with gadolinium to act as dual T1/T2 contrast agents for magnetic resonance imaging (MRI). Parameters such as size, stability, morphology, and magnetic behavior were evaluated by a detailed characterization analysis. To assess their efficacy in imaging and therapy, relaxivity and hyperthermia experiments were performed, respectively. The results revealed that both synthetic methods lead to SPIONs with similar average size, 9 nm. Mössbauer spectroscopy indicated that samples obtained from MR/P consist of approximately 11-13% of Fe present in magnetite, while samples obtained from MpH have higher contents of 33-45%. Despite coating and functionalization, all samples exhibited superparamagnetic behavior at room temperature. Hyperthermia experiments showed increased SAR values with higher magnetic field intensity and frequency. Moreover, the relaxivity studies suggested potential dual T1/T2 contrast agent capabilities for the coated SPpH-Dx-Au-Gd sample, thus demonstrating its potential in cancer diagnosis.

Assessment of two non-invasive techniques for measuring turbulent benthic fluxes in a shallow lake.

Benthic fluxes refer to the exchange rates of nutrients and other compounds between the water column and the sediment bed in aquatic ecosystems. Their quantification contributes to our understanding of aquatic ecosystem functioning. Near-bed hydrodynamics plays an important role at the sediment-water interface, especially in shallow lakes, but it is poorly considered by traditional measuring techniques of flux quantification, such as sediment incubations. Thus, alternative sampling techniques are needed to characterize key benthic fluxes under in-situ hydrodynamic conditions. This study aimed to evaluate the performance of two promising methods: relaxed eddy accumulation (REA) and mass transfer coefficient (MTC). We applied them in a hyper-eutrophic shallow lake to measure the fluxes of ammonium, phosphate, iron, and manganese ions. For the first time, REA revealed hourly nutrient flux variations, indicating a strong lake biogeochemical dynamics at short time-scales. Daily average fluxes are of similar orders of magnitude for REA and MTC for ammonium (24 and 42 mmol m2 d-1), manganese (1.0 and 0.8), and iron (0.8 and 0.7) ions. They are one order of magnitude higher than fluxes estimated from sediment incubations, due to the difficulty in reproducing in-situ oxygen and hydrodynamic conditions in the laboratory. Although the accuracy of both techniques needs to be improved, the results revealed their potential: REA follows the short-term biogeochemical dynamics of sediments, while MTC could be widely used for lake monitoring because of its simpler implementation.

Influenza vaccination accuracy among adults: Self-report compared with electronic health record data.

OBJECTIVE: To assess the validity of electronic health record (EHR)-based influenza vaccination data among adults in a multistate network. METHODS: Following the 2018-2019 and 2019-2020 influenza seasons, surveys were conducted among a random sample of adults who did or did not appear influenza-vaccinated (per EHR data) during the influenza season. Participants were asked to report their influenza vaccination status; self-report was treated as the criterion standard. Results were combined across survey years. RESULTS: Survey response rate was 44.7% (777 of 1740) for the 2018-2019 influenza season and 40.5% (505 of 1246) for the 2019-2020 influenza season. The sensitivity of EHR-based influenza vaccination data was 75.0% (95% confidence interval [CI] 68.1, 81.1), specificity 98.4% (95% CI 92.9, 99.9), and negative predictive value 73.9% (95% CI 68.0, 79.3). CONCLUSIONS: In a multistate research network across two recent influenza seasons, there was moderate concordance between EHR-based vaccination data and self-report.

Unveiling the Antiviral Capabilities of Targeting Human Dihydroorotate Dehydrogenase against SARS-CoV-2.

The urgent need for effective treatments against emerging viral diseases, driven by drug-resistant strains and new viral variants, remains critical. We focus on inhibiting the human dihydroorotate dehydrogenase (HsDHODH), one of the main enzymes responsible for pyrimidine nucleotide synthesis. This strategy could impede viral replication without provoking resistance. We evaluated naphthoquinone fragments, discovering potent HsDHODH inhibition with IC50 ranging from 48 to 684 nM, and promising in vitro anti-SARS-CoV-2 activity with EC50 ranging from 1.2 to 2.3 µM. These compounds exhibited low toxicity, indicating potential for further development. Additionally, we employed computational tools such as molecular docking and quantitative structure-activity relationship (QSAR) models to analyze protein-ligand interactions, revealing that these naphthoquinones exhibit a protein binding pattern similar to brequinar, a potent HsDHODH inhibitor. These findings represent a significant step forward in the search for effective antiviral treatments and have great potential to impact the development of new broad-spectrum antiviral drugs.

High-Precision Viral Detection Using Electrochemical Kinetic Profiling of Aptamer-Antigen Recognition in Clinical Samples and Machine Learning.

High-precision viral detection at point of need with clinical samples plays a pivotal role in the diagnosis of infectious diseases and the control of a global pandemic. However, the complexity of clinical samples that often contain very low viral concentrations makes it a huge challenge to develop simple diagnostic devices that do not require any sample processing and yet are capable of meeting performance metrics such as very high sensitivity and specificity. Herein we describe a new single-pot and single-step electrochemical method that uses real-time kinetic profiling of the interaction between a high-affinity aptamer and an antigen on a viral surface. This method generates many data points per sample, which when combined with machine learning, can deliver highly accurate test results in a short testing time. We demonstrate this concept using both SARS-CoV-2 and Influenza A viruses as model viruses with specifically engineered high-affinity aptamers. Utilizing this technique to diagnose COVID-19 with 37 real human saliva samples results in a sensitivity and specificity of both 100 % (27 true negatives and 10 true positives, with 0 false negative and 0 false positive), which showcases the superb diagnostic precision of this method.

Framework for policymaking on self-management of health by older adults using technologies.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, the use of information and communication technologies (ICTs) to support care management exponentially increased. Governments around the world adapted existing programs to meet the needs of patients. The reactivity of governments, however, led to changes that were inequitable, undermining groups such as older adults living with chronic diseases and disability. Policies that align with recent developments in ICTs can promote better health outcomes and innovation in care management. A framework for policymaking presents potential for overcoming barriers and gaps that exist in current policies. OBJECTIVE: The goal of this study was to examine how well a provisional framework for policymaking represented the interactions between various components of government policymaking on older adults' self-management of chronic disease and disability using ICTs. METHODS: Through an online survey, the study engaged policymakers from various ministries of the government of Ontario in the evaluation and revision of the framework. The data were analyzed using simple statistics and by interpreting written comments. RESULTS: Nine participants from three ministries in the government of Ontario responded to the questionnaire. Overall, participants described the framework as useful and identified areas for improvement and further clarification. A revised version of the framework is presented. CONCLUSIONS: Through the revision exercise, our study confirmed the relevance and usefulness for a policymaking framework on the self-management of disease and disability of older adults' using ICTs. Further inquiries should examine the application of the framework to jurisdictions other than Ontario considering the dissociated nature of Canadian provincial healthcare systems.

Mortality risk after COVID-19 vaccination: A self-controlled case series study.

BACKGROUND: Although previous studies found no-increased mortality risk after COVID-19 vaccination, residual confounding bias might have impacted the findings. Using a modified self-controlled case series (SCCS) design, we assessed the risk of non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes after primary series COVID-19 vaccination. METHODS: We analyzed all deaths between December 14, 2020, and August 11, 2021, among individuals from eight Vaccine Safety Datalink sites. Demographic characteristics of deaths in recipients of COVID-19 vaccines and unvaccinated individuals were reported. We conducted SCCS analyses by vaccine type and death outcomes and reported relative incidences (RI). The observation period for death spanned from the dates of emergency use authorization to the end of the study period (August 11, 2021) without censoring the observation period upon death. We pre-specified a primary risk interval of 28-day and a secondary risk interval of 14-day after each vaccination dose. Adjusting for seasonality in mortality analyses is crucial because death rates vary over time. Deaths among unvaccinated individuals were included in SCCS analyses to account for seasonality by incorporating calendar month in the models. RESULTS: For Pfizer-BioNTech (BNT162b2), RIs of non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes were below 1 and 95 % confidence intervals (CIs) excluded 1 across both doses and both risk intervals. For Moderna (mRNA-1273), RI point estimates of all outcomes were below 1, although the 95 % CIs of two RI estimates included 1: cardiac-related (RI = 0.78, 95 % CI, 0.58-1.04) and non-COVID-19 cardiac-related mortality (RI = 0.80, 95 % CI, 0.60-1.08) 14 days after the second dose in individuals without pre-existing cancer and heart disease. For Janssen (Ad26.COV2.S), RIs of four cardiac-related death outcomes ranged from 0.94 to 0.98 for the 14-day risk interval, and 0.68 to 0.72 for the 28-day risk interval and 95 % CIs included 1. CONCLUSION: Using a modified SCCS design and adjusting for temporal trends, no-increased risk was found for non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes among recipients of the three COVID-19 vaccines used in the US.

How do microplastics alter molluscicidal activity? Effects of weathered microplastics and niclosamide in developing freshwater snails.

Despite the wide distribution and persistence of microplastics (MPs), their interactive effects with molluscicides are unknown. Schistosomiasis, a neglected tropical disease, affects 236.6 million people worldwide. Niclosamide (NCL) is the only molluscicide recommended by the World Health Organization (WHO) and it is used to control the population of Schistosoma spp.'s intermediate host. Thus, this study aimed to evaluate of the interaction between polyethylene (PE) MPs and NCL, and their associated toxicity in the freshwater snail Biomphalaria glabrata (Say 1818). Weathered PE MPs were characterized and theoretical analysis of NCL-MP adsorption nature was made using quantum mechanical calculations. The toxicity of NCL isolated (0.0265 to 0.0809 mg L-1) and under interaction with PE MPs (3400 µg L-1) in B. glabrata embryos and newly hatched snails was analyzed. In silico analysis confirmed the adsorption mechanisms of NCL into PE MPs. PE MPs decreased the NCL toxicity to both B. glabrata developmental stages, increasing their survival and NCL lethal concentrations, indicating concerns regarding NCL use as molluscicide in aquatic environments polluted by MPs. In conclusion, MPs may change the efficiency of chemicals used in snail control programs.

Latent Tuberculosis Infection Testing Practices in a Large US Integrated Healthcare System.

BACKGROUND: Tuberculosis (TB) is a public health threat, with >80% of active TB in the United States occurring due to reactivation of latent TB infection (LTBI). We may be underscreening those with high risk for LTBI and overtesting those at lower risk. A better understanding of gaps in current LTBI testing practices in relation to LTBI test positivity is needed. METHODS: This study, conducted between 1 January 2008 and 31 December 2019 at Kaiser Permanente Southern California, included individuals aged ≥18 years without a history of active TB. We examined factors associated with LTBI testing and LTBI positivity. RESULTS: Among 3 816 884 adults (52% female, 37% White, 37% Hispanic, mean age 43.5 years [standard deviation, 16.1]), 706 367 (19%) were tested for LTBI, among whom 60 393 (9%) had ≥1 positive result. Among 1 211 971 individuals who met ≥1 screening criteria for LTBI, 210 025 (17%) were tested for LTBI. Factors associated with higher adjusted odds of testing positive included male sex (1.32; 95% confidence interval, 1.30-1.35), Asian/Pacific Islander (2.78, 2.68-2.88), current smoking (1.24, 1.20-1.28), diabetes (1.13, 1.09-1.16), hepatitis B (1.45, 1.34-1.57), hepatitis C (1.54, 1.44-1.66), and birth in a country with an elevated TB rate (3.40, 3.31-3.49). Despite being risk factors for testing positive for LTBI, none of these factors were associated with higher odds of LTBI testing. CONCLUSIONS: Current LTBI testing practices may be missing individuals at high risk of LTBI. Additional work is needed to refine and implement screening guidelines that appropriately target testing for those at highest risk for LTBI.

Effect of landscape irrigation regulations on runoff volume from low-density residential catchments during two California droughts.

The severe drought in California (2012-2016) generated significant public and government concern. State and local watering regulations were enacted to reduce residential and commercial water-use during the droughts. This study presents a comparison of residential runoff volumes before and after local landscape irrigation regulations were enacted during the droughts of 2008 and 2012-2016. Each sampling site (Folsom 1 and Folsom 2) was a storm drain outfall that drained a low-density residential catchment in the City of Folsom. Dry season runoff measured at the sampling sites represents neighborhood outdoor water waste, mainly from landscape irrigation. During the drought of 2012-2016, median runoff flows were significantly reduced after local landscape irrigation regulations were enacted. The daily runoff pattern was also highly influenced by regulation, with reductions of daily peak runoff flows on 4-5 days in a week after watering regulations were enacted. The number of peak flow events in the daily runoff pattern were reduced during this period. In addition, a significant reduction in mean runoff volume occurred. Based on these results, the watering regulations enacted by the City of Folsom had a positive effect on reducing urban runoff from residential neighborhoods during the dry season. As the results are from monitoring sites in a relatively small geographical area, further work should evaluate reductions in irrigation runoff from other California locations to determine if this is a localized phenomenon.

Reaching "The Other Half": Teacher Referral Increases Inclusivity in Intervention Research for Neurodivergent School-Age Children.

OBJECTIVE: Researchers employed two recruitment strategies in a school-based comparative effectiveness trial for students with a diagnosis of attention-deficit/hyperactivity disorder (ADHD) or autism. This study assessed the: 1) effectiveness of school-based referrals for identifying students meeting diagnostic criteria and 2) impact of eliminating requirements for existing diagnoses on recruitment, sample characteristics, and intervention response. METHOD: Autistic students and students with ADHD in schools serving underresourced communities were recruited for an executive functioning (EF) intervention trial over 2 years. In Year 1, school staff nominated students with previous diagnoses. In Year 2, school staff nominated students demonstrating EF challenges associated with ADHD or autism; previous diagnosis was not required. Study staff then confirmed diagnoses. RESULTS: More students were included in Year 2 (N = 106) than Year 1 (N = 37). In Year 2, 96% of students referred by school staff met diagnostic criteria for ADHD or autism, 53% of whom were not previously diagnosed. Newly identified students were less likely than previously diagnosed students to be receiving services and, for those with ADHD, were more likely to speak primarily Spanish at home. Previously diagnosed and newly identified students did not differ on other demographic variables or intervention response. Caregivers of previously diagnosed students reported more symptoms than caregivers of newly identified students for both diagnostic groups. Previously diagnosed students with ADHD had more researcher-rated symptoms than newly identified students. CONCLUSIONS: Recruitment for an intervention study using behavior-based referrals from school staff enhanced enrollment without compromising the sample's diagnostic integrity and engaged children who otherwise would have been excluded.

Microcarrier-based fluorescent yeast estrogen screen assay for fast determination of endocrine disrupting compounds.

The presence of endocrine-disrupting compounds (EDCs) in water poses a significant threat to human and animal health, as recognized by regulatory agencies throughout the world. The Yeast Estrogen Screen (YES) assay is an excellent method to evaluate the presence of these compounds in water due to its simplicity and capacity to assess the bioaccessible forms/fractions of these compounds. In the presence of a compound with estrogenic activity, Saccharomyces cerevisiae cells, containing a lacZ reporter gene encoding the enzyme ß-galactosidase, are induced, the enzyme is synthesised, and released to the extracellular medium. In this work, a YES-based approach encompassing the use of a lacZ reporter gene modified strain of S. cerevisiae, microcarriers as solid support, and a fluorescent substrate, fluorescein di-ß-d-galactopyranoside, is proposed, allowing for the assessment of EDCs' presence after only 2 h of incubation. The proposed method provided an EC50 of 0.17 ± 0.03 nM and an LLOQ of 0.03 nM, expressed as 17ß-estradiol. The assessment of different EDCs provided EC50 values between 0.16 and 1.2 × 103 nM. After application to wastewaters, similar results were obtained for EDCs screening, much faster, compared to the conventional 45 h spectrophotometric procedure using a commercial kit, showing potential for onsite high-throughput screening of environmental contamination.

Mixed mucinous adenocarcinoma/large cell neuroendocrine carcinoma of the uterine cervix: case report and molecular characterization of a rare entity.

Mixed neuroendocrine-non-neuroendocrine carcinomas of the cervix are rare and generally aggressive diseases. They often present at an advanced stage with hematogenous or lymphatic metastases. The prognosis is poor, mostly influenced by the neuroendocrine component. Unfortunately, the rarity of the disease caused a lack of information about its pathogenesis and molecular landscape. The latest guidelines recommend a multimodal approach that usually includes radical surgery, platinum/etoposide-based chemotherapy, or chemoradiation. Here, we are presenting a case of metastatic mixed adenocarcinoma-large cell neuroendocrine carcinoma of the cervix in a 49-year-old female patient. The molecular characterization of the lesion highlighted the ubiquitous presence of human papillomavirus-18 DNA both in the adenocarcinomatous and the neuroendocrine components, suggesting a role for the virus in the pathogenesis. Moreover, a different set of mutations was detected in the two parts, thus ruling out a possible clonal evolution of the neuroendocrine component from the adenocarcinoma one. More studies are needed to clarify the molecular landscape of these rare lesions and identify putative targets for therapy.

Racial and ethnic disparities in influenza vaccination coverage among pregnant women in the United States: The contribution of vaccine-related attitudes.

OBJECTIVE: Racial and ethnic disparities in influenza vaccination coverage among pregnant women in the United States have been documented. This study assessed the contribution of vaccine-related attitudes to coverage disparities. METHODS: Surveys were conducted following the 2019-2020 and 2020-2021 influenza seasons in a US research network. Using electronic health record data to identify pregnant women, random samples were selected for surveying; non-Hispanic Black women and influenza-unvaccinated women were oversampled. Regression-based decomposition analyses were used to assess the contribution of vaccine-related attitudes to racial and ethnic differences in influenza vaccination. Data were combined across survey years, and analyses were weighted and accounted for survey design. RESULTS: Survey response rate was 41.2% (721 of 1748) for 2019-2020 and 39.3% (706 of 1798) for 2020-2021. Self-reported influenza vaccination was higher among non-Hispanic White respondents (79.4% coverage, 95% CI 73.1%-85.7%) than Hispanic (66.2% coverage, 95% CI 52.5%-79.9%) and non-Hispanic Black (55.8% coverage, 95% CI 50.2%-61.4%) respondents. For all racial and ethnic groups, a high proportion (generally >80%) reported being seen for care, recommended for influenza vaccination, and offered vaccination. In decomposition analyses, vaccine-related attitudes (e.g., worry about vaccination causing influenza; concern about vaccine safety and effectiveness) explained a statistically significant portion of the observed racial and ethnic disparities in vaccination. Maternal age, education, and health status were not significant contributors after controlling for vaccine-related attitudes. CONCLUSIONS: In a setting with relatively high influenza vaccination coverage among pregnant women, racial and ethnic disparities in coverage were identified. Vaccine-related attitudes were associated with the disparities observed.

Quantifying online citizen science: Dynamics and demographics of public participation in science.

Citizen scientists around the world are collecting data with their smartphones, performing scientific calculations on their home computers, and analyzing images on online platforms. These online citizen science projects are frequently lauded for their potential to revolutionize the scope and scale of data collection and analysis, improve scientific literacy, and democratize science. Yet, despite the attention online citizen science has attracted, it remains unclear how widespread public participation is, how it has changed over time, and how it is geographically distributed. Importantly, the demographic profile of citizen science participants remains uncertain, and thus to what extent their contributions are helping to democratize science. Here, we present the largest quantitative study of participation in citizen science based on online accounts of more than 14 million participants over two decades. We find that the trend of broad rapid growth in online citizen science participation observed in the early 2000s has since diverged by mode of participation, with consistent growth observed in nature sensing, but a decline seen in crowdsourcing and distributed computing. Most citizen science projects, except for nature sensing, are heavily dominated by men, and the vast majority of participants, male and female, have a background in science. The analysis we present here provides, for the first time, a robust 'baseline' to describe global trends in online citizen science participation. These results highlight current challenges and the future potential of citizen science. Beyond presenting our analysis of the collated data, our work identifies multiple metrics for robust examination of public participation in science and, more generally, online crowds. It also points to the limits of quantitative studies in capturing the personal, societal, and historical significance of citizen science.