Dissipation and Risk Assessment of Propaquizafop in Ginseng under Field Conditions.

Propaquizafop is a highly efficient aryloxy phenoxy propionate chiral herbicide. However, the use of propaquizafop, including its safe use methods, residue patterns, dietary risk assessment, and maximum residue limits, for ginseng, a traditional Chinese medicinal plant, has not been studied. An analytical method was established for the simultaneous determination of propaquizafop and its four metabolites in ginseng soil, fresh ginseng, ginseng plant, and dried ginseng using HPLC-MS/MS. This approach showed good linearity (R2 ranging from 0.9827 to 0.9999) and limit of quantification ranging from 0.01 to 0.05 mg/kg. The intra- and interday recovery rates of this method ranged from 71.6 to 107.1% with relative standard deviation ranging from 1.3 to 23.2%. The method was applied to detect residual samples in the field, and it was found that the degradation of propaquizafop in ginseng plants and soil followed a first-order kinetic equation. R2 was between 0.8913 and 0.9666, and the half-life (t1/2) ranged from 5.04 to 8.05 days, indicating that it was an easily degradable pesticide (T1/2 < 30 days). The final propaquizafop residues in ginseng soil, plants, fresh ginseng, and dried ginseng ranged from 0.017 to 0.691 mg/kg. A dietary risk assessment was conducted on the final propaquizafop residue in fresh and dried ginseng. The results showed that the chronic exposure risk quotient values were less than 100% for fresh and dried ginseng (1.15% for fresh ginseng and 1.13% for dried ginseng). This illustrates that the dietary risk associated with the use of 10% propaquizafop emulsifiable concentrate in ginseng is very low. Thus, applying 750 mL/ha of propaquizafop on ginseng could not pose an unacceptable risk to public health. The results of the present study support the registration of propaquizafop in ginseng.

Residue behavior and consumer risk assessment of spirotetramat and chlorpyrifos on cabbage heads and cropped soil.

A field experiment following good agricultural practices was laid out to study the dissipation of spirotetramat (90 g a.i. ha-1 and 180 g a.i. ha-1) and chlorpyrifos (400 g a.i. ha-1 and 800 g a.i. ha-1) on cabbage heads and soil. Samples were processed using quick, easy, cheap, effective, rugged, and safe (QuEChERS) method for residue estimation of spirotetramat and chlorpyrifos, which were further detected using HPLC-PDA and GC-FPD respectively. The residues of spirotetramat on cabbage heads reached below detection limit (BDL) (< 0.05 mg kg-1) on 7th and 10th day and for chlorpyrifos, BDL (< 0.01 mg kg-1) was achieved on 10th and 15th day for X and 2X dose, respectively. On 20th day after second spray, residues in soil were found to be BDL for both the pesticides. Half-life of spirotetramat and chlorpyrifos was found to be 3 and 2 days, respectively while a safe pre-harvest interval (PHI) of 9 days for spirotetramat and 10 days for chlorpyrifos is suggested on cabbage. The dietary risk assessment studies for various age groups of Indian population, ascertained safety of treated cabbage heads for consumption, as current study revealed that hazard quotient (HQ) < 1 and theoretical maximum dietary intake (TMDI) < maximum permissible intake (MPI) for both the pesticides at respective PHI.

Measurement of the12C(p,n)12N reaction cross section below 150 MeV.

Objective. Proton therapy currently faces challenges from clinical complications on organs-at-risk due to range uncertainties. To address this issue, positron emission tomography (PET) of the proton-induced11C and15O activity has been used to provide feedback on the proton range. However, this approach is not instantaneous due to the relatively long half-lives of these nuclides. An alternative nuclide,12N (half-life 11 ms), shows promise for real-timein vivoproton range verification. Development of12N imaging requires better knowledge of its production reaction cross section.Approach. The12C(p,n)12N reaction cross section was measured by detecting positron activity of graphite targets irradiated with 66.5, 120, and 150 MeV protons. A pulsed beam delivery with 0.7-2 × 108protons per pulse was used. The positron activity was measured during the beam-off periods using a dual-head Siemens Biograph mCT PET scanner. The12N production was determined from activity time histograms.Main results. The cross section was calculated for 11 energies, ranging from 23.5 to 147 MeV, using information on the experimental setup and beam delivery. Through a comprehensive uncertainty propagation analysis, a statistical uncertainty of 2.6%-5.8% and a systematic uncertainty of 3.3%-4.6% were achieved. Additionally, a comparison between measured and simulated scanner sensitivity showed a scaling factor of 1.25 (±3%). Despite this, there was an improvement in the precision of the cross section measurement compared to values reported by the only previous study.Significance. Short-lived12N imaging is promising for real-timein vivoverification of the proton range to reduce clinical complications in proton therapy. The verification procedure requires experimental knowledge of the12N production cross section for proton energies of clinical importance, to be incorporated in a Monte Carlo framework for12N imaging prediction. This study is the first to achieve a precise measurement of the12C(p,n)12N nuclear cross section for such proton energies.

An integrated methodology for quality assessment of therapeutic antibodies with potential long circulation half-life in harvested cell culture fluid using FcRn immobilized hydrophilic magnetic graphene.

Designing modified therapeutic antibodies with enhanced FcRn-binding affinity holds promise in the extension of circulation half-lives and potential refinement of pharmacokinetics. During the development of these new-generation therapeutic antibodies, FcRn binding affinity of IgGs is emphasized and monitored as a critical quality attribute (CQA), alongside other critical assessments including titer and aggregation level. However, the traditional workflow for assessing the overall quality of expressed IgGs in harvested cell culture fluid (HCCF) is blamed to be cumbersome and time-consuming. This study presents an integrated methodology for the rapid quality assessment of IgGs in HCCF by selectively extracting IgGs with favorable high FcRn affinity for subsequent analysis using size exclusion chromatography (SEC). The approach utilizes innovative adsorbents known as FcRn immobilized hydrophilic magnetic graphene (MG@PDA@PAMAM-FcRn) in a magnetic solid-phase extraction (MSPE) process. To simulate the in vivo binding dynamics, MSPE binding and dissociation was performed at pH 6.0 and 7.4, respectively. The composite have demonstrated enhanced extraction efficiency and impurity removal ability in comparison to commercially available magnetic beads. The SEC monomer peak area value provides the output of this method, the ranking of which enabled the facile identification of superior HCCF samples with high overall quality of IgG. Optimization of MSPE parameters was performed, and the method was validated for specificity, precision, sensitivity, and accuracy. The proposed method exhibited an analytical time of 0.6 h, which is 7-22 times shortened in comparison to the conventional workflow.

Influence of Half-life and Smoking/Nonsmoking Ratio on Biomarker Consistency between Waves 1 and 2 of the Population Assessment of Tobacco and Health Study.

BACKGROUND: Biomarkers of exposure are tools for understanding the impact of tobacco use on health outcomes if confounders like demographics, use behavior, biological half-life, and other sources of exposure are accounted for in the analysis. METHODS: We performed multiple regression analysis of longitudinal measures of urinary biomarkers of alkaloids, tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, volatile organic compounds (VOC), and metals to examine the sample-to-sample consistency in Waves 1 and 2 of the Population Assessment of Tobacco and Health (PATH) Study including demographic characteristics and use behavior variables of persons who smoked exclusively. Regression coefficients, within- and between-person variance, and intra-class correlation coefficients (ICC) were compared with biomarker smoking/nonsmoking population mean ratios and biological half-lives. RESULTS: Most biomarkers were similarly associated with sex, age, race/ethnicity, and product use behavior. The biomarkers with larger smoking/nonsmoking population mean ratios had greater regression coefficients related to recency of exposure. For VOC and alkaloid metabolites, longer biological half-life was associated with lower within-person variance. For each chemical class studied, there were biomarkers that demonstrated good ICCs. CONCLUSIONS: For most of the biomarkers of exposure reported in the PATH Study, for people who smoke cigarettes exclusively, associations are similar between urinary biomarkers of exposure and demographic and use behavior covariates. Biomarkers of exposure within-subject consistency is likely associated with nontobacco sources of exposure and biological half-life. IMPACT: Biomarkers measured in the PATH Study provide consistent sample-to-sample measures from which to investigate the association of adverse health outcomes with the characteristics of cigarettes and their use.

Residue behaviour and health risk assessment of chlorpyrifos and mancozeb in apple fruits and soil.

Mancozeb residue estimation was done using second derivative ultraviolet spectroscopy by Shimadzu ultraviolet-visible spectrophotometer, and chlorpyrifos was estimated by QuEChERS technique using GC-FPD. The persistence for chlorpyrifos was carried out at two locations, and for mancozeb, persistence studies were carried out at four locations. Initial deposits of mancozeb on apple fruits ranged from 1.33 to 1.63 mg/kg at the recommended dose and from 2.55 to 3.26 mg/kg at double the recommended dose at all four locations. Chlorpyrifos residues in apple fruits had an initial deposit of 0.94-0.99 mg/kg at recommended dose and 1.75-1.92 mg/kg at double the recommended dose. Mancozeb residues in apple fruit were below the detection limit (BDL) after 20 days at recommended dose and after 25 days at double the recommended dose at two locations, while mancozeb residue at the other two locations and the residues of chlorpyrifos at all locations reached BDL after 15 and 20 days at recommended and double the recommended doses, respectively. Half-life of mancozeb varied from 3.07 to 4.02 days at recommended dose and from 3.30 to 4.32 days at double the recommended dose, whereas chlorpyrifos residues dissipated to half their initial concentration on 2.33-2.35 days at recommended dose and 2.89-2.90 days at double the recommended dose. The soil samples showed no presence of residues of chlorpyrifos and mancozeb at harvest. The risk assessment revealed that hazard quotient for the intake of mancozeb was in the range of 0.06-0.13% and 0.20-0.44% for rural and urban population, while for the intake of chlorpyrifos, hazard quotient was in the range of 0.10-0.12% for rural population and 0.33-0.38% for urban population, and theoretical maximum dietary intake (9.67 × 10-5 mg/person and 3.18 × 10-4 mg/person for rural population and urban population in case of mancozeb and 3.22 × 10-5 mg/person and 1.06 × 10-4 mg/person for rural population and urban population in case of chlorpyrifos) was also found to be less than maximum permissible intake (1.38 mg/kg for mancozeb and 0.60 mg/kg for chlorpyrifos). The results of risk assessment thereby indicated that apple consumption does not pose a risk to human health.

Safety Evaluation of Chlorantraniliprole in Lychee Based on Residue and Dietary Risk Assessment.

This report presents the development of a highly effective method employing high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to investigate chlorantraniliprole's dissipation, risk assessment, and residue distribution in whole lychee fruit and its pulp. Mean recoveries of the samples ranged from 80 to 105%, exhibiting a relative standard deviation (RSD) of below 8%. The limits of quantification (LOQ) for lychee and pulp were determined as 0.001 mg/kg, and half-lives (t1/2) ranged from 8.0 to 12.2 days. Terminal residue concentrations in whole litchi and pulp were determined as 0.008-0.45 mg/kg and ≤0.001 mg/kg. These residues were treated twice and thrice at two different dosage levels with pre-harvest intervals (PHIs) of 7, 14, and 21 days. The potential chronic risk posed by chlorantraniliprole to humans was non-negligible, as indicated by the risk quotient (RQ) value not exceeding 1. Therefore, this study provides significant fresh data about the safe application of chlorantraniliprole in the production of lychee, which will help China develop maximum residual limits (MRLs).

Prognostic value of CA125 kinetics, half-life, and nadir in the treatment of epithelial ovarian cancer: a systematic review and meta-analysis.

OBJECTIVE: To investigate the prognostic value of cancer antigen 125 (CA125) related variables on progression free survival and overall survival in primary and recurrent ovarian cancers. METHOD: A comprehensive review of the Medline, Embase, and Cochrane Library databases was conducted to identify relevant literature on survival outcomes according to the ELIMination Rate Constant K (KELIM), Gynecologic Cancer InterGroup (GCIG) CA125 response criteria, CA125 half-life, and CA125 nadir levels during first line or later line chemotherapy. The search included articles published before February 2023. Cut-off values determining the favorable/unfavorable score of each study were extracted, and pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed using a random effects model to identify the relationship between survival outcomes of the favorable/unfavorable groups, which was determined by an individual model using CA125 kinetics. RESULTS: A total of 27 studies with 14 444 patients with epithelial ovarian cancer were included in this meta-analysis. In primary ovarian cancer, a favorable KELIM score, determined by individual modeled cut-off values, was associated with a significant progression free survival (HR 0.53, 95% CI 0.45 to 0.62) and overall survival (HR 0.51, 95% CI 0.43 to 0.62) benefit in the primary setting. The favorable KELIM scored group also correlated with a better progression free survival (HR 0.54, 95% CI 0.47 to 0.62) in relapsed disease. We failed to demonstrate a better prognostic value of the GCIG response criteria and the CA125 half-life for progression free survival and overall survival. CONCLUSION: Novel chemotherapy response scores, such as KELIM, may be more clinically relevant than other prognostic models using CA125 kinetics, being directly associated with a more favorable survival in both the primary and relapsed setting in patients with epithelial ovarian cancer. STUDY REGISTRATION: The systemic review and meta-analysis were registered in PROSPERO (CRD42023385512).

Dissipation behavior and dietary risk assessment of cyclaniliprole and its metabolite in cabbage under field conditions.

Cyclaniliprole, a novel diamide insecticide, can successfully control Spodoptera litura (Fabricius, 1775) in cabbage. Understanding the residual level of cyclaniliprole in crops and the risk related to its dietary intake is imperative for safe application. Here, we established a simplified, sensitive method for simultaneous analysis of cyclaniliprole and its metabolite NK-1375 (3-bromo-2-((2-bromo-4H-pyrazolo[1,5-d]pyrido[3,2-b]-[1,4]oxazin-4-ylidene)amino)-5-chloro-N-(1-cyclopropylethyl)benzamide) in cabbage by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to investigate their dissipation behavior and residual characteristics. Cyclaniliprole showed rapid dissipation in cabbage and had a half-life of 1.8-2.7 days. The highest residue of total cyclaniliprole (sum of cyclaniliprole and NK-1375) in cabbage from different pre-harvest intervals (3 and 5 days) was 0.25 mg/kg. Our results confirmed the generally low dietary risk quotient of cyclaniliprole (0.243-1.036%) among different age and gender groups in China. Therefore, cyclaniliprole did not pose an unacceptable risk to consumers. This study contributes to setting cyclaniliprole maximum residue limit in cabbage by assessing its dissipation fate and food safety risks.

Dissipation and Dietary Risk Assessment of Prochloraz in Strawberries under Greenhouse Conditions.

Prochloraz and its metabolites in strawberries have not been determined until now. Meanwhile, few reports in the literature have concerned the dissipation behavior and risk assessment of prochloraz and its metabolites in strawberries under greenhouse conditions in Beijing. A method for the determination of prochloraz and its metabolites in strawberries was developed using QuEChERS in combination with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Prochloraz and its metabolites recovered from strawberries were present in concentrations of 73.06% to 116.01%, their RSDs ranged from 1.12% to 9.17%, and their limits of detection ranged from 0.1 to 1 µg kg-1. Then, a study was conducted on the dissipation of prochloraz in strawberries under greenhouse conditions. The dissipation of prochloraz in strawberries followed the first-order kinetic equation, and its half-life was 8.06 days. The health risk associated with prochloraz in strawberries was evaluated using the target hazard quotient (THQ) method and EFSA PRIMo model. The results showed that the THQ values, %ARfD values, and %ADI values were less than 1. These results indicate that no health concerns of prochloraz are associated with the consumption of the studied strawberries. The government can use the results of this study to support the establishment of a maximum residue level for prochloraz in strawberries.

Healthcare costs among hemophilia A patients in the United States treated with rurioctocog alfa pegol (FVIII-PEG) or antihemophilic factor (recombinant), FC fusion protein (rFVIIIFc) using real-world data.

AIMS: To compare healthcare costs in patients with non-inhibitor hemophilia A treated with Rurioctocog Alfa Pegol (FVIII-PEG) versus Antihemophilic Factor (Recombinant), FC Fusion Protein (rFVIIIFc). MATERIALS AND METHODS: Administrative claims data from the Merative MarketScan Commercial (Commerical) and Medicaid (Medicaid) databases were used for these analyses. Males with non-inhibitor hemophilia A treated with FVIII-PEG or rFVIIIFc from 1 January 2016 to 31 March 2021 were identified (earliest treatment = index). Patients were required to have continuous database enrollment for six months before and after the index date. Follow-up was variable in length until disenrollment or study end. All-cause and hemophilia-related healthcare costs were reported per-patient per month [PPPM] and the average weekly dose during follow-up was compared between treatment groups. Generalized linear regressions were used to estimate multivariable-adjusted differences in total costs and weekly dosage in the two treatment groups. RESULTS: A total of 131 FVIII-PEG (66 Commercial; 65 Medicaid) and 204 rFVIIIFc (111 Commercial; 93 Medicaid) patients were eligible. Mean age was 20.5 and 24.4 for FVIII-PEG and rFVIIIFc in Commercial and 14.9 and 17.5 for FVIII-PEG and rFVIIIFc in Medicaid. PPPM mean (standard deviations [SD]) total healthcare costs in Commercially insured patients were $35,868 [$21,717] for FVIII-PEG vs $40,424 [$25,882] for rFVIIIFc. Costs in Medicaid were $27,495 [$23,243] for FVIII-PEG vs $30,237 [$28,430] for rFVIIIFc. After adjusting for baseline characteristics, the costs for rFVIIIFc (vs FVIII-PEG) were higher by $5,215 in Commercial and $3,895 in Medicaid, but the differences were not statistically significant (p > 0.05). Similar findings were observed for hemophilia-specific healthcare costs. The adjusted mean weekly dose was 6,047 vs 4,892 IU, p = 0.21 for FVIII-PEG vs rFVIIIFc in Commercial and 5,549 vs 7,228 IU, p = 0.07 for FVIII-PEG vs rFVIIIFc in Medicaid. CONCLUSIONS: Healthcare costs and treatment dosing were similar (p > 0.05) for non-inhibitor hemophilia A patients treated with FVIII-PEG and rFVIIIFc.

Dissipation kinetics, decontamination, consumer risk assessment and monitoring of flonicamid and imidacloprid residues in capsicum under open field and polyhouse condition.

Liquid chromatography mass spectrometry (LC-MS)-based detection of flonicamid, imidacloprid and 6-chloronicotinic acid residues was validated and analysed in capsicum fruit, processed products and soil. The standard concentrations (0.0025 to 0.25 µg mL-1) of insecticides had a good linear curve (r2>0.99). Limit of detection and limit of quantification values were 0.0025 and 0.01 mg kg-1, respectively. The accuracy (80.53 to 100.33 %) of capsicum matrices and soil (89.41 to 100.52 %) and precision (RSD <10%) were established. Dissipation of imidacloprid (20 and 40 g a.i. ha-1) and flonicamid (75 and 150 g a.i. ha-1) at single (X) and double dose (2X) was studied under open field and polyhouse conditions. Under open field conditions, the flonicamid and imidacloprid residues persisted with half-life of 1.98, 2.90 days (X) and 2.80, 3.14 (2X) days, respectively. While under polyhouse conditions, the flonicamid and imidacloprid residues persisted with a half-life of 2.84, 3.66 (X) and 3.24, 3.97 (2X) days, respectively. The metabolite, 6-CNA, was not detected in any samples under open field and polyhouse condition. Among decontamination treatments, cooking in boiling water for 10 minutes reduced 78 to 81.60 percent of imidacloprid and flonicamid residues in both doses. The estimated dietary risk assessment of imidacloprid and flonicamid residues (RQ <1) indicated that the risk is within the acceptable limit. In farmgate capsicum samples, residues of flonicamid (7 samples) and imidacloprid (11 samples) were detected. Market samples of capsicum products (powder, flakes and sauce) were not detected with residues of selected insecticides.

Stabilization of Enzymes by Using Thermophiles.

Manufactured steroid compounds have many applications in the pharmaceutical industry. Due to the chemical complexity and chirality of steroids, there is an increasing demand for enzyme-based bioconversion processes to replace those based on chemical synthesis. In this context, thermostability of the involved enzymes is a highly desirable property as both the increased half-life of the enzyme and the enhanced solubility of substrates and products will improve the yield of the reactions. Metagenomic libraries from thermal environments are potential sources of thermostable enzymes of prokaryotic origin, but the number of expected hits could be quite low for enzymes handling substrates such as steroids, rarely found in prokaryotes. An alternative to metagenome screening is the selection of thermostable variants of well-known steroid-processing enzymes. Here we review and detail a protocol for such selection, where error-prone PCR (epPCR) is used to introduce random mutations into a gene to create a variants library for further selection of thermostable variants in the thermophile Thermus thermophilus. The method involves the use of folding interference vectors where the proper folding of the enzyme of interest at high temperature is linked to the folding of a reporter encoding a selectable property such as thermostable resistance to kanamycin, leading to a life-or-death selection of variants of reinforced folding independently of the activity of the enzyme.

Assessment of pharmacokinetics, safety, and tolerability following twice-daily administration of molnupiravir for 10 days in healthy participants.

Molnupiravir is an orally administered, small-molecule ribonucleoside prodrug of ß-D-N4-hydroxycytidine (NHC) that has demonstrated potent, broad-spectrum preclinical activity against RNA viruses and has a high barrier to the development of resistance. A double-blind, placebo-controlled, phase I trial was conducted to evaluate the pharmacokinetics (PKs), safety, and tolerability of 10.5-day administration of multiple doses of molnupiravir and its metabolites in healthy, adult participants. Participants were randomly assigned (3:1) to receive molnupiravir (400 mg [n = 6], 600 mg [n = 6], and 800 mg [n = 12]) or matching placebo (n = 8) every 12 h (q12h) for 10.5 days. Blood was collected to evaluate the PKs of NHC in plasma and of its active metabolite, NHC-triphosphate (NHC-TP), in peripheral blood mononuclear cells (PBMCs). Molnupiravir was generally well-tolerated. All adverse events were mild or moderate in severity and none led to treatment discontinuation. No clinically meaningful dose-related safety findings were observed. Mean time to maximal concentration was ~1.50 to 1.98 h for plasma NHC and ~4.00 to 8.06 h for PBMC NHC-TP. Accumulation was minimal (<1.2) for NHC and ~2- to 2.5-fold for NHC-TP. Plasma NHC PKs was generally dose proportional, and PBMC NHC-TP PKs was less than dose proportional over the dose range studied. NHC and NHC-TP PK support twice-daily administration. Overall, molnupiravir administered at up to 800 mg q12h for 10.5 days was generally well-tolerated in healthy participants with dose-linear PKs, supporting the evaluation of longer molnupiravir dosing up to 10 days in future clinical trials.

Dissipation, residue, and dietary risk assessment of dimethachlon in grapes.

Dimethachlon, a dicarboximide fungicide, has gained widespread usage in Asian countries. While considered a low-toxicity fungicide, concerns regarding potential health effects, such as nephrotoxicity, have emerged. To date, neither China nor other countries have established maximum residue limit (MRL) for dimethachlon on grapes, and exposure risk assessment of dimethachlon is lacking. Here, we developed a QuEChERS method coupled with gas chromatography-mass spectrometry (GC-MS) to investigate the dissipation rates and terminal residues of dimethachlon in grapes, along with an assessment of dietary risk to consumers. Our results indicated that the average recoveries of dimethachlon in grapes ranged from 74 to 76%. The limit of quantification (LOQ) was 0.050 mg/kg. After undergoing 112 days of storage at -18 °C, the dissipation rate of dimethachlon in grapes was found to be less than 30%, suggesting a state of stable storage. In the context of good agricultural practice (GAP) guidelines, the half-lives of dimethachlon in grapes were 14.3-18.1 days, which is notably longer compared to the reported values for other crops. The terminal residues of dimethachlon in grapes at 14 and 21 days were found to be < 0.05-0.53 mg/kg and < 0.05-0.29 mg/kg, respectively. Regarding the dietary risk assessment, the calculated risk quotient (RQ) value was significantly below 100%, indicating a negligible chronic risk of dimethachlon in grapes at the recommended dosage. This study provides an important reference for the analysis of dimethachlon and offers valuable empirical data to support the establishment of MRL.

Does knowledge have a half-life? An observational study analyzing the use of older citations in medical and scientific publications.

OBJECTIVES: In the process of scientific progress, prior evidence is both relied on and supplanted by new discoveries. We use the term 'knowledge half-life' to refer to the phenomenon in which older knowledge is discounted in favour of newer research. By quantifying the knowledge half-life, we sought to determine whether research published in more recent years is preferentially cited over older research in medical and scientific articles. DESIGN: An observational study employing a directed, systematic search of current literature. DATA SOURCES: BMJ, PNAS, JAMA, NEJM, The Annals of Internal Medicine, The Lancet, Science and Nature were searched. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eight high-impact medical and scientific journals were sampled examining original research articles from the first issue of every year over a 25-year span (1996-2020). The outcome of interest was the difference between the publication year of the article and references cited, termed 'citation lag'. DATA EXTRACTION AND SYNTHESIS: Analysis of variance was used to identify significant differences in citation lag. RESULTS: A total of 726 articles and 17 895 references were included with a mean citation lag of 7.5±8.4 years. Across all journals, >70% of references had been published within 10 years of the citing article. Approximately 15%-20% of referenced articles were 10-19 years old, and articles more than 20 years old were cited infrequently. Medical journals articles had references with significantly shorter citation lags compared with general science journals (p≤0.01). Articles published before 2009 had references with significantly shorter citation lags compared with those published in 2010-2020 (p<0.001). CONCLUSIONS: This study found evidence of a small increase in the citation of older research in medical and scientific literature over the past decade. This phenomenon deserves further characterisation and scrutiny to ensure that 'old knowledge' is not being lost.

Dissipation, residue distribution, and risk assessment of ethiprole and its metabolites in rice under various open field conditions.

BACKGROUND: Ethiprole has been registered to control planthoppers in rice fields for many years in Asia. However, its dissipation and residues in rice under natural field conditions and health hazards are largely unclear. In the present study, a modified QuEChERS (i.e. Quick Easy Cheap Effective Rugged Safe) and high-performance liquid chromatography-tandem mass spectrometry method was established to detect ethiprole and its metabolites, ethiprole amide and ethiprole sulfone, in brown rice, rice husks, and rice straw. The field experiments were implemented in 12 representative provinces of China under Good Agricultural Practices aiming to investigate the fate and terminal residues of ethiprole and its metabolites in rice. Finally, the dietary risk of ethiprole was evaluated. RESULTS: The average recoveries of these analytes in all matrices were 86.4-99.0% with a repeatability of 0.575-9.38%. The limits of quantification for each compound were 0.01 mg kg-1 . Dissipation of ethiprole followed the single first-order, first + first-order, and first-order multi-compartment kinetic models with a half-life of 2.68-8.99 days in rice husks. The dissipation half-life of ethiprole combining all metabolites was 5.20-16.2 days in rice husks. The terminal residues of ethiprole and its metabolites at preharvest intervals of 21 days were < 0.011, 0.25, and 0.20 mg kg-1 in brown rice, rice husks, and rice straw, respectively. Ethiprole amide was undetectable in all matrices, and the risk quotient of ethiprole was far less than 100%. CONCLUSION: Ethiprole rapidly converted to ethiprole sulfone in rice, and ethiprole and ethiprole sulfone mainly remained in rice husks and straws. The dietary risk of ethiprole was acceptable for Chinese consumers. © 2023 Society of Chemical Industry.

Dissipation Dynamic, Residue Distribution and Risk Assessment of Emamectin Benzoate in Longan by High-Performance Liquid Chromatography with Fluorescence Detection.

A derivatization method combined with high-performance liquid chromatography-fluorescence detection (HPLC-FLD) was used to evaluate the dissipation, residue distribution and risk assessment of emamectin benzoate in whole longan and pulp. The average recoveries were 82-111% with relative standard deviation (RSD) less than 11%. The limit of quantification (LOQ) was 0.001 mg/kg in longan and pulp. The half-lives were 3.3-4.2 days. The terminal residues in whole longan were <0.001-0.025 mg/kg applied two and three times at two levels of dosage with PHIs of 10, 14, and 21 days. The residues in whole longan had a higher quantity than those in the pulp, and the terminal residues of pulp were all lower than LOQ (0.001 mg/kg). The chronic risk of emamectin benzoate was not negligible to humans depending on ADI% value, which was higher than 1; and the acute risk was acceptable to the consumer. This study could provide guidance for the safe use of emamectin benzoate in longan and serve as a reference for the establishment of maximum residue limits (MRLs) in China.

Behavior of trifloxystrobin and propineb as combination product in tomato (Solanum lycopersicum) and their risk assessment for human health.

Fungicides have their own unique characteristics and modes of action; a combination formulation [combination product (combi product)] of trifloxystrobin and propineb was applied to tomatoes for their dissipation kinetics and to ensure consumer safety. The combi product was applied at a 10-day interval with standard (61.25 + 1072.75 g a.i. ha-1 ) and double (122.5 + 2145.50 g a.i. ha-1 ) doses. The efficient analytical method was established using the quick, easy, cheap, effective, rugged, and safe (QuEChERS) approach followed by LC-MS. The maximum residue levels of 0.15 and 0.35 mg kg-1 of trifloxystrobin were detected in tomato fruits immediately after application at standard and double doses, respectively. The corresponding levels of propineb as carbon disulfide were 0.47 and 0.90 mg kg-1 , respectively. Considering trifloxystrobin (0.7 mg kg-1 ) codex maximum residue limit and propineb as dithiocarbamate (3.0 mg kg-1 ) European Commission maximum residue limit in tomato, a pre-harvest interval of 1 day can be proposed. The anticipated residue contributions of both fungicides were far less than the acceptable daily intake. The targeted hazard quotient and hazard index were also less than 1 for both fungicides. Furthermore, the theoretical maximum residue contribution was less than its maximum permissible intake, which indicates that the consumption of tomatoes containing the measured value of each fungicide residue could not pose any health risks.

Determination of chlorantraniliprole 18.5% SC in the paddy ecosystem and its risk assessment.

Chlorantraniliprole belongsto theanthranilic diamide group is widely used against broad range of lepidopteron pests in a variety of vegetable and rice pests includingyellow rice stem borer and leaf folder. Supervised field trials were conducted duringRabi (2018-2019) and Kharif (2019) to evaluate the dissipation pattern and risk assessment of chlorantraniliprole 18.5% SC in paddy ecosystem following foliar application at 30 and 60 g a.i. ha-1 in two different cropping seasons.Modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) technique was used for the extraction of CAP residues with acetonitrile and determined by LC-MS/MS (ESI +).The limit of quantification (LOQ) was 0.01 µg g-1 for paddy leaf, straw, husk, and brown rice, respectively and 0.005 µg g-1 for soil. The average recoveries obtained were 84.30-88.92% from paddy leaf, 94.25-97.81% from straw, 90.21-93.38% from husk, 93.57-96.40% from brown rice and 89.93-91.14% from soil. The residues in paddy leaf dissipated within 35-40 days with a half-life of 4.33-5.07 days in Rabi and 3.92-4.86 days in Kharif at 30 and 60 g a.i. ha-1, respectively. The residues in soil dissipated within 15-21 days with a half-life of 14.44-15.75 days in Rabi and 13.33-14.44 days in Kharif at respective doses. At harvest chlorantraniliprole residues were not detected in straw, husk, and brown rice. The dietary risk of paddy leaf (green fodder) for cattle was found safe for consumption as the hazard index is less than one. Soil ecological risk assessment was found to be less than one (RQ < 0.1) for earthworms (Eisenia foetida) and arthropods (Aphidiusrhopalosiphi). The presentmethod could be useful inthe analysis ofchlorantraniliproleresidues in different cereals and vegetable crop ecosystems and application at recommended dose is safe for the final produce at harvest.