Analysis of pancreatic cancer treatment and survival disparities in Florida throughout the Covid-19 pandemic.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is currently the third-leading cause of cancer-related death in the United States. African Americans (AAs) with PDAC have worse survival in comparison to other racial groups. The COVID-19 pandemic caused significant stress to the healthcare system. We aim to evaluate the pandemic's impact on already known disparities in newly diagnosed patients with PDAC in Florida. METHODS: This is a retrospective analysis of newly diagnosed patients with PDAC in the OneFlorida+ Data Trust based upon date of diagnosis: Pre-pandemic (01/01/2017- 09/30/2019), Transition (10/01/2019-02/28/2020), and Pandemic (03/1/2020-10/31/2020). Primary endpoints are time to treatment initiation and rate of surgery and secondary endpoint is survival time. Disparities due to age, sex, race, and income were also evaluated. Chi-squared or Fisher's exact test when necessary, Kruskal-Wallis test, and Kaplan-Meier analysis with log-rank test were performed to compare the differences between the comparative groups for categorical, quantitative, and survival outcomes, respectively. Multivariable regression analyses were conducted to estimate the effects of cofactors. RESULTS: 934 patients with a median age of 67 years were included. There were 47.8% females and 52.2% males; 19.4% AA, 70.2% Caucasian, 10.4% Other race; median income was $53,551. While we observed a significant reduction in the diagnosis rate of new PDAC cases during the pandemic, there were no significant differences in demographic distributions among the three cohorts. Time to treatment did not significantly change from the pre-pandemic to the pandemic, and no difference was observed across all demographics. Rate of surgery increased significantly from the pre-pandemic (35.8%) to the pandemic (55.6%). AAs in the pre-pandemic cohort had a significantly lower rate of surgery of 25.0% compared to 41.7% in Caucasians. AAs, patients ≥ 67 years, and income < $53,000 had significantly higher hazards to death and shorter median survival time (mST). CONCLUSIONS: While no differences in time to initial treatment are observed among the newly diagnosed PDAC patients, there remain significant disparities in the rate of surgery and overall survival. Observing a significant reduction in diagnosis rate and analyzing disparities can provide insight into the effect of a resource-restricting pandemic for patients with newly diagnosed PDAC.

Disposition and Follow-up for Low-Risk Febrile Infants: A Secondary Analysis of a Multicenter Study.

OBJECTIVE: American Academy of Pediatrics guidelines recommend that febrile infants at low risk for invasive bacterial infection be discharged from the emergency department (ED) if primary care provider (PCP) follow-up occurs within 24 hours. We aimed to (1) assess the association between having electronic health record (EHR) documentation of a PCP and ED disposition and (2) describe documentation of potential barriers to discharge and plans for post-discharge follow-up in low-risk febrile infants. METHODS: We conducted a secondary analysis of a multicenter, cross-sectional study of low-risk febrile infants. Descriptive statistics characterized ED disposition on the basis of the day of the visit, EHR documentation of PCP, scheduled or recommended PCP follow-up, and barriers to discharge. RESULTS: Most infants (3565/4042, 90.5%) had EHR documentation of a PCP. Compared with discharged infants, a similar proportion of hospitalized infants had EHR documentation of PCP (90.3% vs 91.2%, P = .47). Few infants (1.5%) had barriers to discharge documented. Of the 3360 infants (83.1%) discharged from the ED, 1544 (46.0%) had documentation of scheduled or recommended 24-hour PCP follow-up. Discharged infants with weekday visits were more likely than those with weekend visits to have documentation of scheduled or recommended 24-hour follow-up (50.0% vs 35.5%, P < .001). CONCLUSIONS: Most infants had a documented PCP, yet fewer than half had documentation of a scheduled or recommended 24-hour follow-up. A dedicated focus on determining post-ED care plans that are safe and patient-centered may improve the quality of care for this population.

Dissection of genetic architecture of nine hazardous component traits of mainstream smoke in tobacco (Nicotiana tabacum L.).

Tobacco (Nicotiana tabacum L.) use is the leading cause of preventable death, due to deleterious chemical components and smoke from tobacco products, and therefore reducing harmful chemical components in tobacco is one of the crucial tobacco breeding targets. However, due to complexity of tobacco smoke and unavailability of high-density genetic maps, the genetic architecture of representative hazardous smoke has not been fully dissected. The present study aimed to explore the genetic architecture of nine hazardous component traits of mainstream smoke through QTL mapping using 271 recombinant inbred lines (RILs) derived from K326 and Y3 in multiple environments. The analysis of genotype and genotype by environment interaction (GE) revealed substantially greater heritability over 95% contributed mostly by GE interaction effects. We also observed strong genetic correlations among most studied hazardous smoke traits, with the highest correlation coefficient of 0.84 between carbon monoxide and crotonaldehyde. Based on a published high-density genetic map, a total of 19 novel QTLs were detected for eight traits using a full QTL model, of which 17 QTLs showed significant additive effects, six showed significant additive-by-environment interaction effects, and one pair showed significant epistasis-by-environment interaction effect. Bioinformatics analysis of sequence in QTL region predicted six genes as candidates for four traits, of which Nt21g04598.1, Nt21g04600.1, and Nt21g04601.1 had pleiotropic effects on PHE and TAR.

Gene-based association tests in family samples using GWAS summary statistics.

Genome-wide association studies (GWAS) have led to rapid growth in detecting genetic variants associated with various phenotypes. Owing to a great number of publicly accessible GWAS summary statistics, and the difficulty in obtaining individual-level genotype data, many existing gene-based association tests have been adapted to require only GWAS summary statistics rather than individual-level data. However, these association tests are restricted to unrelated individuals and thus do not apply to family samples directly. Moreover, due to its flexibility and effectiveness, the linear mixed model has been increasingly utilized in GWAS to handle correlated data, such as family samples. However, it remains unknown how to perform gene-based association tests in family samples using the GWAS summary statistics estimated from the linear mixed model. In this study, we show that, when family size is negligible compared to the total sample size, the diagonal block structure of the kinship matrix makes it possible to approximate the correlation matrix of marginal Z scores by linkage disequilibrium matrix. Based on this result, current methods utilizing summary statistics for unrelated individuals can be directly applied to family data without any modifications. Our simulation results demonstrate that this proposed strategy controls the type 1 error rate well in various situations. Finally, we exemplify the usefulness of the proposed approach with a dental caries GWAS data set.

Perspectives of the Friedreich ataxia community on gene therapy clinical trials.

Gene therapy is a potential treatment for Friedreich ataxia, with multiple programs on the horizon. The purpose of this study was to collect opinions about gene therapy from individuals 14 years or older with Friedreich ataxia or parents/caregivers of Friedreich ataxia patients who were diagnosed as children 17 or younger. Participants were asked to complete a survey after reading brief educational materials regarding gene therapy. Most of the patients captured in this survey have an early-onset (classical) presentation of the disease. Participants expressed urgency in participating in gene therapy clinical trials despite the associated risks. About half of the respondents believed that gene therapy would cease progression or minimize symptoms, whereas nearly one-fourth expected to be cured. The survey also revealed how participants perceive their symptom burden, because a substantial majority reported that balance/walking issues most interfere with their quality of life and would be the symptom they would prioritize treating. Although not statistically significant, more caregivers prioritized treating cardiomyopathy than patients. This study provides valuable information on priorities, beliefs, and expectations regarding gene therapy and serves to guide future gene therapy opinion studies and gene therapy trial design.

Malachite green: a long-buried water-soluble AIEgen with near-infrared fluorescence for living cell nucleus staining.

Fluorescent imaging probes are crucial for exploring nucleus-related cellular events in live cells. Ideal probes should be photostable, small-sized, highly contrasted, and low in background. Here, we discovered that malachite green is a water-soluble near-infrared luminogen with aggregation-induced emission properties. Importantly, it can be used for living cell nucleus staining in a wash-free manner.

MOVER-R and Penalized MOVER-R Confidence Intervals for the Ratio of Two Quantities.

Developing a confidence interval for the ratio of two quantities is an important task in statistics because of its omnipresence in real world applications. For such a problem, the MOVER-R (method of variance recovery for the ratio) technique, which is based on the recovery of variance estimates from confidence limits of the numerator and the denominator separately, was proposed as a useful and efficient approach. However, this method implicitly assumes that the confidence interval for the denominator never includes zero, which might be violated in practice. In this article, we first use a new framework to derive the MOVER-R confidence interval, which does not require the above assumption and covers the whole parameter space. We find that MOVER-R can produce an unbounded confidence interval, just like the well-known Fieller method. To overcome this issue, we further propose the penalized MOVER-R. We prove that the new method differs from MOVER-R only at the second order. It, however, always gives a bounded and analytic confidence interval. Through simulation studies and a real data application, we show that the penalized MOVER-R generally provides a better confidence interval than MOVER-R in terms of controlling the coverage probability and the median width.

Effective Removal of Boron from Aqueous Solutions by Inorganic Adsorbents: A Review.

Increasing levels of boron in water exceeding acceptable thresholds have triggered concerns regarding environmental pollution and adverse health effects. In response, significant efforts are being made to develop new adsorbents for the removal of boron from contaminated water. Among the various materials proposed, inorganic adsorbents have emerged as promising materials due to their chemical, thermal, and mechanical stability. This review aims to comprehensively examine recent advances made in the development of inorganic adsorbents for the efficient removal of boron from water. Firstly, the adsorption performance of the most used adsorbents, such as magnesium, iron, aluminum, and individual and mixed oxides, are summarized. Subsequently, diverse functionalization methods aimed at enhancing boron adsorption capacity and selectivity are carefully analyzed. Lastly, challenges and future perspectives in this field are highlighted to guide the development of innovative high-performance adsorbents and adsorption systems, ultimately leading to a reduction in boron pollution.