Search

Quinazolinone synthesis usually requires employing sensitive substrates, hazardous solvents, large excess oxidants, and expensive catalysts. In this study, an efficient and environmentally benign pathway was developed to synthesize 2-phenylquinazolin-4(3H)-one via oxidative coupling between commercially available and stable chemicals, including 2-aminobenzamide and benzyl alcohol without toxic oxidizing agents and transition-metal catalysts. A high yield of the desired product (up to 84%) was obtained at 120°C for 24 h in the presence of oxygen as a green oxidant and t-BuONa as a base. Importantly, the study scope was expanded toward successfully producing various 2-phenylquinazolin-4(3H)-one derivatives in moderate-to-good yields. Furthermore, control experiments proposed that the conversion involved the initial partial oxidation of benzyl alcohol to the benzaldehyde intermediate under basic conditions, followed by the condensation, intramolecular nucleophilic addition, and oxidative dehydrogenation to 2-phenylquinazolin-4(3H)-one.

Quantification of motor symptom progression in Parkinsons disease (PD) patients is crucial for assessing disease progression and for optimizing therapeutic interventions, such as dopaminergic medications and deep brain stimulation. Cumulative and heuristic clinical experience has identified various clinical signs associated with PD severity, but these are neither objectively quantifiable nor robustly validated. Video-based objective symptom quantification enabled by machine learning (ML) introduces a potential solution. However, video-based diagnostic tools often have implementation challenges due to expensive and inaccessible technology, and typical black-box ML implementations are not tailored to be clinically interpretable. Here, we address these needs by releasing a comprehensive kinematic dataset and developing an interpretable video-based framework that predicts high versus low PD motor symptom severity according to MDS-UPDRS Part III metrics. This data driven approach validated and robustly quantified canonical movement features and identified new clinical insights, not previously appreciated as related to clinical severity, including pinkie finger movements and lower limb and axial features of gait. Our framework is enabled by retrospective, single-view, seconds-long videos recorded on consumer-grade devices such as smartphones, tablets, and digital cameras, thereby eliminating the requirement for specialized equipment. Following interpretable ML principles, our framework enforces robustness and interpretability by integrating (1) automatic, data-driven kinematic metric evaluation guided by pre-defined digital features of movement, (2) combination of bi-domain (body and hand) kinematic features, and (3) sparsity-inducing and stability-driven ML analysis with simple-to-interpret models. These elements ensure that the proposed framework quantifies clinically meaningful motor features useful for both ML predictions and clinical analysis.

BackgroundSome hormonally active cancers have low survival rates, but a large proportion of their incidence remains unexplained. Endocrine disrupting chemicals may affect hormone pathways in the pathology of these cancers.ObjectiveTo evaluate cross-sectional associations between per- and polyfluoroalkyl substances (PFAS), phenols, and parabens and self-reported previous cancer diagnoses in the National Health and Nutrition Examination Survey (NHANES).MethodsWe extracted concentrations of 7 PFAS and 12 phenols/parabens and self-reported diagnoses of melanoma and cancers of the thyroid, breast, ovary, uterus, and prostate in men and women (≥20 years). Associations between previous cancer diagnoses and an interquartile range increase in exposure biomarkers were evaluated using logistic regression models adjusted for key covariates. We conceptualized race as social construct proxy of structural social factors and examined associations in non-Hispanic Black, Mexican American, and other Hispanic participants separately compared to White participants.ResultsPrevious melanoma in women was associated with higher PFDE (OR:2.07, 95% CI: 1.25, 3.43), PFNA (OR:1.72, 95% CI: 1.09, 2.73), PFUA (OR:1.76, 95% CI: 1.07, 2.89), BP3 (OR: 1.81, 95% CI: 1.10, 2.96), DCP25 (OR: 2.41, 95% CI: 1.22, 4.76), and DCP24 (OR: 1.85, 95% CI: 1.05, 3.26). Previous ovarian cancer was associated with higher DCP25 (OR: 2.80, 95% CI: 1.08, 7.27), BPA (OR: 1.93, 95% CI: 1.11, 3.35) and BP3 (OR: 1.76, 95% CI: 1.00, 3.09). Previous uterine cancer was associated with increased PFNA (OR: 1.55, 95% CI: 1.03, 2.34), while higher ethyl paraben was inversely associated (OR: 0.31, 95% CI: 0.12, 0.85). Various PFAS were associated with previous ovarian and uterine cancers in White women, while MPAH or BPF was associated with previous breast cancer among non-White women.Impact statementBiomarkers across all exposure categories (phenols, parabens, and per- and poly- fluoroalkyl substances) were cross-sectionally associated with increased odds of previous melanoma diagnoses in women, and increased odds of previous ovarian cancer was associated with several phenols and parabens. Some associations differed by racial group, which is particularly impactful given the established racial disparities in distributions of exposure to these chemicals. This is the first epidemiological study to investigate exposure to phenols in relation to previous cancer diagnoses, and the first NHANES study to explore racial/ethnic disparities in associations between environmental phenol, paraben, and PFAS exposures and historical cancer diagnosis.

Phthalates with potential adverse health effects are being replaced by other phthalates or phthalate alternatives. Little is known about temporal trends of phthalate exposure in pregnant women in the United States. We quantified 16 metabolites of eight phthalates and di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) in 656 urine samples collected from 192 California pregnant women in 2007-2013 during their second and third trimesters of pregnancy who participated in the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) study. We used multiple regression to estimate least squares geometric means of phthalate biomarker concentrations and annual percent changes over the study period. Biomarker concentrations of diethyl phthalate (DEP) and three phthalates with known toxicity and adverse health effects (i.e., butyl benzyl phthalate [BBzP], dibutyl phthalate [DBP], di(2-ethylhexyl) phthalate [DEHP]) decreased, while those of di-isobutyl phthalate [DiBP], di-isononyl phthalate [DiNP], and di-n-octyl phthalate [DOP] increased in California pregnant women during our study period. To understand broad social forces that may influence temporal trends and geographic variations in phthalate exposure across countries, we compared our phthalate biomarker concentrations with those of other populations. We observed over a factor of 2 differences in exposure across countries for some phthalate biomarkers and between pregnant and nonpregnant women for DEP.

ObjectivesThis study aims to assess the impact of Health Resources and Services Administration (HRSA) investment in oral health through the HRSA FY16 Oral Health Service Expansion (OHSE) funding on workforce, access, and quality in health centers (HCs) from 2015 to 2017.MethodsAnalyses were conducted using data from the Uniform Data System from 2015 and 2017, and the 2015 Area Health Resource File. Change in indicators of oral health workforce, access, and quality of care by the receipt of OHSE funding received by HCs in 2016 were examined. Regression models for 1,345 HCs were developed to conduct a difference-in-difference analyses of the comparative change from 2015 to 2017 in the dependent variables among OHSE and non-OHSE awardees while controlling for confounders.ResultsOHSE awardees showed a significant difference in the oral health workforce with a higher mean number increase by 0.6 full time equivalent (FTE) dentists, 0.4 dental hygienists, 1.1 dental assistants, and 2.3 for other dental staff compared to non-OHSE awardees. Compared to non-OHSE awardees, OHSE awardees showed a mean increase of 712 dental patients served who received 1,402 dental visits, representing a 9-percentage point increase in the percentage of HCs that had an oral health program and a 3-percentage point increase in the ratio of dental patients to total patients.ConclusionsFunding dedicated to oral health service expansion in HCs may result in outcomes ranging from increasing workforce to reduction in access and financial barriers. Retrospective analysis demonstrated improved capacity for oral healthcare delivery attributable to HRSA support to HCs.

BackgroundThe choice of malaria treatment for HIV-infected pregnant women receiving efavirenz-based antiretroviral therapy must consider the potential impact of drug interactions on antimalarial exposure and clinical response. The aim of this study was to investigate the effects of efavirenz on artemether-lumefantrine (AL) because no studies have isolated the impact of efavirenz for HIV-infected pregnant women.MethodsA prospective clinical pharmacokinetic (PK) study compared HIV-infected, efavirenz-treated pregnant women with HIV-uninfected pregnant women in Tororo, Uganda. All women received the standard 6-dose AL treatment regimen for Plasmodium falciparum malaria with intensive PK samples collected over 21 days and 42-days of clinical follow-up. PK exposure parameters were calculated for artemether, its active metabolite dihydroartemisinin (DHA), and lumefantrine to determine the impact of efavirenz.ResultsNine HIV-infected and 30 HIV-uninfected pregnant women completed intensive PK evaluations. Relative to controls, concomitant efavirenz therapy lowered the 8-hour artemether concentration by 76% (P = 0.013), DHA peak concentration by 46% (P = 0.033), and day 7 and 14 lumefantrine concentration by 61% and 81% (P = 0.046 and 0.023), respectively. In addition, there were nonsignificant reductions in DHA area under the concentration-time curve0-8hr (35%, P = 0.057) and lumefantrine area under the concentration-time curve0-∞ (34%, P = 0.063) with efavirenz therapy.ConclusionsPregnant HIV-infected women receiving efavirenz-based antiretroviral therapy during malaria treatment with AL showed reduced exposure to both the artemisinin and lumefantrine. These data suggest that malaria and HIV coinfected pregnant women may require adjustments in AL dosage or treatment duration to achieve exposure comparable with HIV-uninfected pregnant women.

Summary: Background/Aims: With polarizing income disparities, this study investigated the prevalence and trends of liver disease in a U.S. population‐based sample based on income‐to‐poverty ratio (IPR). Methods: This cross‐sectional study analysed survey data from the 1999–2018 National Health and Nutrition Examination Survey with highest (HIG), middle‐income (MIG), and lowest income (LIG) groups defined as IPR ≤ 1, 1 < IPR <5, and IPR ≥ 5, respectively. Results: We analysed 59,204 adult participants with 48.2% male, 39.7% aged 18–39, 36.2% 40–59, and 24.1% ≥60 years. The weighted prevalence of hepatitis C (HCV), B (HBV) infection, non‐alcoholic fatty liver disease (NAFLD), alcohol‐associated liver disease (ALD), and advanced fibrosis in LIG were 3.9% (n = 276), 7.4% (n = 527), 33.2% (n = 714), 5.2% (n = 401), and 9.0% (n = 694), respectively, compared to lower rates for HIG: 1.0% (n = 82), 3.2% (n = 263), 29.6% (n = 798), 3.9% (n = 354), and 5.0% (n = 638). After adjusting for age, sex, race and ethnicity, education, and birthplace, HIG had the lowest odds of having any liver disease [adjusted odds ratio (aOR) 0.67, p < 0.0001], with similar findings for specific conditions including HCV, HBV, and advanced fibrosis (aOR 0.24, 0.52, and 0.64, all p < 0.0001, respectively). While viraemic HCV prevalence decreased over time for HIG, there were no changes for MIG nor LIG. Similarly, NAFLD prevalence was stable for HIG but increased for MIG and LIG. Conclusion: LIG and MIG in the United States have higher liver disease burdens than HIG, with increasing NAFLD prevalence and lack of decline in current HCV infection prevalence over time as opposed to declining or stable trend in HIG. [ABSTRACT FROM AUTHOR]

Introduction: Chronic liver disease (CLD) is associated with increased morbidity and mortality. Understanding health disparities can inform appropriate interventions. We aimed to study mortality outcomes of those with CLD by the income level (income-to-poverty ratio <5 as lower income and ≥5 as higher income). Methods: In this retrospective cohort study, we analyzed data of adults from the National Health and Nutrition Examination Survey, 1999–2018. CLD included viral hepatitis, nonalcoholic fatty liver disease (NAFLD), and alcohol-associated liver disease (ALD). Results: We analyzed 59,204 adults: 47,224 without CLD and 11,980 with CLD. The CLD group was older, more likely male, racial/ethnic minority groups or foreign-born, and had lower educational and income levels (p < 0.001). Most (80.02%) CLD participants did not have college degrees and had lower income (79.18%). Among CLD participants, similar differences were observed between lower and higher income groups. Lower income participants with CLD had significantly higher 10-year cumulative mortality compared to higher income CLD participants (15.26 vs. 8.00%, p < 0.001), with consistent findings in viral hepatitis and NAFLD subgroups (p < 0.001) but not ALD (p = 0.71). Adjusting for age, sex, race, birthplace, lower income CLD participants were 2.01 (hazard ratio [HR]: 2.01; 95% CI: 1.79–2.26) times more likely to die overall and in viral hepatitis (HR: 2.05; 95% CI: 1.31–3.24) and NAFLD subgroups (HR: 2.32; 95% CI: 1.69–3.18) but not ALD (HR: 1.17; 95% CI: 0.55–2.51). Conclusion: Lower income, foreign-born, and racial/ethnic minority groups were disproportionately represented among those with CLD, with lower income and CLD individuals having double the mortality risk compared to their higher income counterparts. Interventions should be culturally appropriate and address socioeconomic barriers. [ABSTRACT FROM AUTHOR]

Herein, we present an efficient, one‐pot reaction for accessing 3‐benzylated indoles via the coupling of benzyl alcohols with indoles under heterogeneous catalysis by manganese ferrite (MnFe2O4) nanoparticles. Notably, this reaction, for the first time, employs MnFe2O4 nanoparticles prepared using a simple grinding method. The high compatibility of MnFe2O4 nanoparticles enables a broad substrate scope and high regioselectivity. Moreover, this approach offers several attractive highlights including the use of a recyclable oxide catalyst and green and cost‐effective alkylating reagents under solvent‐free conditions. [ABSTRACT FROM AUTHOR]

Green and highly selective synthesis of ammonia (NH3) via electrochemical reduction reaction of toxic nitrite (NO2−RR) in a neutral electrolyte is a feasible solution for energy and environmental issues. Dual‐nature electrocatalysts combining metal and metal‐derived materials are crucial for enhancing the selectivity parameter and efficacy of this reaction. Here, Pd‐, Pt‐, Ru‐, and Ir‐decorated Co3(PO4)2 (CoPi) composites with a robust metal–support interaction are obtained via the one‐pot pulsed laser ablation in liquid method. Among the designed composites, Ir–CoPi affords ≈100% Faradaic efficiency, mass balance, and selectivity toward NH3 product at sufficiently low potentials. Further, it affords the highest NH3 yield rate of 19.13 mg h−1 cm−2 with 78.1% removal of toxic NO2− with a rate constant kapp = 0.31 mm min−1 under −1.6 V versus Ag/AgCl. In situ experiments and theoretical investigations reveal the underlying mechanisms responsible for this outstanding performance of Ir–CoPi, which can be accredited to the generation of specific active sites on the Ir component. Insights derived from the evolving intermediate reactive species provide new opportunities for large‐scale NH3 production through electrochemical techniques, density functional theory calculations, and the improvement of the corresponding industrial processes. [ABSTRACT FROM AUTHOR]