The incidence of respiratory depression was much higher in group P (17.78%) than in group R (no patient) and group RP (1.2%). The incidence of adverse events was lower in groups R (4.82%) and RP (9.64%) than in group P (31.11%). The combination of RT and propofol takes effect quickly, makes patients alert quickly, provides a sufficient depth of sedation, reduces body movement, does not inhibit circulation and respiratory function, does not affect sleep, and is the preferred mode for gastroscopy doctors and anesthesiologists.Remimazolam tosilate (RT) is a new short-acting γ-aminobutyric acid A (GABAA) receptors agonist. However, its optimal use mode and dosage still remain unclear. This study aimed to examine the safety and effectiveness of the combination of RT and propofol in gastroscopy. This was a prospective, single-blind, randomized, multicenter, parallel-group study. All eligible 256 patients were randomized into the following 3 groups. Patients were anesthetized with propofol (Group P), RT (Group R) or the combination of RT and propofol (Group RP). The primary efficacy endpoints were: body movement score; satisfaction of gastroscopy doctors; success rate of sedation and effects on sleep status. Sedation induction time, time to be fully alert and adverse events were also recorded. The probability of complete immobility was lower in group R (33.73%) than in group P (86.67%) and RP (83.13%). The rate of doctors’ satisfaction was much lower in group R (28.92%) than in group P (77.78%) and RP (72.29%). The success rate of sedation and sleep outcome score has no difference in the three groups. The time to adequate sedation was longer in group RP (77.27 ± 18.63 s) than in group P (64.47 ± 24.36 s), but much shorter than that in group R (102.84 ± 46.43s). The time to be fully alert was shorter in group R (6.30 ± 1.52 min) and RP (6.54 ± 1.13 min) than in group P (7.87 ± 1.08 min). The proportion of sedative hypotension was significantly higher in group P (41.11%) than in group R (1.20%) and group RP (3.61%) ( Gastroscopy, enteroscopy, and other endoscopic examinations are often difficult for patients to cooperate with and leave an unpleasant impression on patients . The useRemimazolam tosilate (RT) is a new ultrashort-acting benzodiazepine having a high affinity for the GABAA receptor . The GABHowever, the dosage of RT varies greatly for gastroscopy. A single dose of 0.10–0.20 mg/kg was given in some clinical trials . In anothttp://www.chictr.org.cn . The study protocol followed the consolidated standards of reporting trial (CONSORT) guidelines. The whole trial was conducted according to the Declaration of Helsinki and the International Conference on Harmonization of Good Clinical Practice. All participating centers obtained approval from the institutional review board for participation. Written informed consent was obtained from patients undergoing upper gastrointestinal endoscopy before the start of any protocol-specified procedures.This study was approved by the Clinical Research Ethics Committee of the Tianjin Medical University General Hospital (IRB2020-YX-040-01) and registered at This was a prospective, single-blind, randomized, multicenter, parallel-group study assessing the efficacy and safety of RT , propofol , and the combination of RT and propofol. The trial was performed at four centers in China.The inclusion criteria were as follows : 18≤ age2 < body mass index (BMI) < 30 kg/m2 , RT (group R), or RT combined with propofol (group RP) within 24 h prior to upper gastrointestinal endoscopy. The central randomization method was used for grouping, with each center competing for admission. The centralized randomization software “91trail” of Aisha medicine was used for the randomization program. The evaluation investigator and the administration investigator were set up in this trial. Besides blinding the patients, the evaluation investigator was also blinded during the whole trial process.The complete routine preparation before gastroscopy included fasting for at least 6 h and discontinuation of water intake for at least 2 h before the surgery. Before the sedation induction, the patients took 10 g lidocaine hydrochloride glue in the throat for about 5 min and slowly swallowed it till they felt that the tongue was enlarged and the throat was numb. Then, the administration investigator administered butorphanol tartrate  5 μg/kg intravenously. After 3 min of butorphanol tartrate administration, an initial intravenous dose of propofol 1.5 mg/kg for group P, RT 7.5 mg for group R, and RT 3.75 mg and propofol 0.75 mg/kg for group RP was administered to patients for the induction of sedation. The upper gastrointestinal endoscopy was initiated when adequate sedation [Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) score ≤3]  was achiThe primary efficacy endpoints included the following : Body moThe secondary outcomes included the following : Sedatio(1) MOAA/S score: MOAA/S score was recorded 1(T1), 1.5 (T1.5), 2(T1.25), 2.5(T2.5), and 3 (T3) min after the initial dose of RT or propofol was administered (recorded as 0 min (T0) at this time), and then every 1 min until the MOAA/S score reached 5 points for three consecutive times. These time points were recorded as T4, T5, T6,T7, T8 and so on.(2) Adverse events: nausea, vomiting, headache, dizziness, somnolence, chills, and injection pain.α = 0.05 and β = 20%, The non-inferiority margin(δ) was 15%. Under these assumptions, each group had a minimum of 67 patients. Considering the potential loss of follow-up (15%), we increased the sample size of each group to 78.Our preliminary study showed that the probability of absolute immobility of propofol during gastroscopy was about 86% in our department. We assumed that the incidence rate of absolute immobility in groups RP and P was about 86%, using a noninferiority test with p value of < 0.05 was considered statistically significant.Calculations were carried out using Statistical Package of Social Science, Windows version 25 , IBM). Descriptive statistics were used to evaluate all data, continuous data were presented with means and standard deviations while numerical data with median and interquartile ranges. Continuous data were compared using ANOVA, if significantly different then using LSD multiple comparison analysis method. Numerical data were compared using a Chi-square test, or the Fisher exact test, as appropriate. All statistical tests were two-sided, and A total of 286 patients from 4 centers who underwent gastroscopy were selected for the study. Of these, 16 patients were excluded because they did not meet the inclusion criteria or meet exclusion criteria. 270 patients were randomized in the ratio of 1:1:1, 12 patients were excluded because of high blood pressure before administration and 2 patients asked to withdraw. So a total of 256 patients were randomly divided into propofol (n = 90), RT (n = 83), and the combination of RT and propofol groups (n = 83). No patients were dropped out during drug administration and the follow-up period. The detailed study flow chart is shown in p > 0.05).The three groups had a good balance in age, sex, ASA score, BMI, and relevant medical history  . No signp < 0.001), with no statistically significant difference between groups P and RP (p > 0.05). The median of the three groups showed complete immobility (group P), slight body movement (group R), and complete immobility (group RP) (The probability of complete immobility was 86.67% (group P), 33.73% (group R), and 83.13% (group RP). The probability of complete immobility in group R was lower than that in group P (p < 0.001) and RP (roup RP) .Moreover, we recorded the MOAA/S score at each time point (T1–T8) . Figure p < 0.001). The median of the three groups showed very satisfied (group P), satisfied (group R), and very satisfied (group RP) (The rate at which the gastroscopy doctors were very satisfied with the anesthetic effect was 77.78% (group P), 28.92% (group R), and 72.29% (group RP) . The ratroup RP) .The success rate of sedation in the three groups was 100% (group P), 97.59% (group R), and 100% (group RP) .The sleep status was assessed using PSQI. The sleep outcome score did not change at baseline and 7 (D7) and 30 (D30) days after gastroscopy .p < 0.001). The time to adequate sedation in group RP was longer than that in group P (p = 0.009). (The time to adequate sedation in the three groups was 64.47 ± 24.36 s (group P), 102.84 ± 46.43 s (group R), and 77.27 ± 18.63 s (group RP) . The tim 0.009). .p < 0.001)and RP (p < 0.001)was shorter than that in group P. However, the time to be fully alert in groups R and RP showed no significant difference , 6.30 ± 1.52 min (group R), and 6.54 ± 1.13 min (group RP) . The timp < 0.001) and RP . No significant difference was observed in the incidence of hypotension between groups R and RP (p = 0.149). The incidence of treatment-related hypotension in group P was 8.89%, which was much higher than that in groups R (no patient) and RP . However, no significant difference was found in hypotension requiring treatment between groups R and RP (p = 0.316).The incidence of hypotension  was signp < 0.001).Besides, the incidence of respiratory depression in group P was 17.78%, which was much higher than that in groups R (no patient) and RP , RT (group R), and the combination of RT and propofol (group RP) in patients undergoing gastroscopy. The findings were as follows . The bodPrevious studies confirmed that RT could be safely and effectively used for sedation in outpatient surgeries, such as gastrointestinal endoscopy , bronchoThis trial was divided into three groups: group P: the initial administration dose of propofol was 1.5 mg/kg; group R: the initial administration dose of RT was 7.5 mg because our previous study  (5 mg RTp < 0.001) and RP (p < 0.001). The median values of the body movement indices in the three groups showed complete immobility (group P), slight body movement (group R), and complete immobility (group RP). The results of this study showed that the probability of being completely immobile during gastroscopy was not significantly different between group P and RP. However, the probability of being completely immobile in group R was significantly lower than that in group P (p < 0.001). The rates of successful sedation in groups P (100%) and R (97.59%) were consistent with the results of previous phase III trials. Also, the rate of successful sedation was 100% in group RP, demonstrating that the gastroscopy could be successfully completed in the three groups. Despite no statistically significant difference in the sedation success rates among the three groups, the gastroscopy doctors preferred to choose the sedation scheme with less body movement (group P and RP).At the same time, the extremely satisfactory rate of the gastroscopy doctors regarding sedation was 77.78% (group P) and 72.29% (group RP), which was significantly higher than that in group R  was longer than that in group P (64.47 ± 24.36 s), but much shorter than that in group R (102.84 ± 46.43 s) and also shorter than that of the previous commonly used sedatives, such as dexmedetomidine  8.6–13  (16 min)The time to being fully alert in group R (6.30 ± 1.52 min) was significantly lower than that in group P (7.87 ± 1.08 min) in this study. The time to being fully alert in group RP was 6.54 ± 1.13 min, which was significantly lower than that in group P and showed no difference compared with group R. It proved that propofol led to deep sedation and the awakening time was longer. The combination of RT and propofol could reduce propofol dosage and, at the same time, achieve sufficient sedation. Therefore, the awakening time was significantly shortened.2 after RT or propofol injection to evaluate the safety of the three sedation methods. The results showed that the incidence of hypotension and hypotension requiring treatment in group P was higher than that in group R, and the incidence of respiratory depression was higher than that in group R. The incidence of hypotension and respiratory depression in group RP was lower than that in group P. It indicated that the administration mode in group RP was safe. Due to the definition of “Sedative hypotension to be treated” is still controversial. So in this trial, “Sedative hypotension to be treated” is decided by anesthesiologist. Because the criteria for administering vasopressors by the same anaesthesiologist was consistent, there was no bias among groups.We also recorded the changes in blood pressure, heart rate, respiratory rate, and SpOAt the same time, we also recorded the adverse events. In this study, 28 patients (31.11%) in group P had adverse events of different types, including nausea, vomiting, headache, dizziness, somnolence, and injection pain (23 patients). However, the combination of RT and propofol could significantly decrease the incidence of adverse events, especially injection pain (one patient), increasing satisfaction level of patients.Despite important findings, this study also had some limitations. For example, we only selected the drug dosage based on the previous results in group RP and carried out preliminary experiments to verify the effectiveness. However, further studies are needed to explore a better drug matching technique. This study did not examine patients aged more than 70 years, patients aged less than 18 years, or patients with a BMI greater than 30, which would be the focus of our subsequent studies.The combination of RT and propofol took effect quickly, made patients alert quickly, provided a sufficient depth of sedation, reduced body movement, did not inhibit circulation and respiratory function, did not affect sleep quality, and was the preferred mode for gastroscopy doctors and anesthesiologists.


In North America, long-term wet deposition has been monitored through two national networks: the Canadian Air and Precipitation Monitoring Network (CAPMoN) and the US National Atmospheric Deposition Program (NADP), for Canada and the USA, respectively. In order to assess the comparability of measurements from the two networks, collocated measurements have been made at two sites, one in each country, since 1986 . In this study, we compared the measurements from NADP and CAPMoN instrumentation at the collocated sites at the Pennsylvania State University (Penn State), USA, from 1989 to 2016, and Frelighsburg, Quebec, Canada, from 2002 to 2019. We also included in the study the collocated daily-vs-weekly measurements by the CAPMoN network during 1999–2001 and 2016–2017 in order to evaluate the differences in wet concentration of ions due to sampling frequency alone. The study serves as an extension to two previous CAPMoN-NADP inter-comparisons by Sirois et al.  and Wetherbee et al., in . At the Penn State University site, for 1986–2019, CAPMoN was higher than NADP for all ions, in terms of weekly concentration, precipitation-weighted annual mean concentration, and annual wet deposition. The precipitation-weighted annual mean concentrations were higher for SO42− (2%), NO3− (12%), NH4+ (16%), H+ (6%), and base cations and Cl− (11–15%). For annual wet deposition, CAPMoN was higher for SO4−2, NO3−, NH4+ and H+ (5–17%), and base cations and Cl− (12–17%) during 1986–2019. At the Frelighsburg site, NADP changed the sample collector in October 2011. For 2002–2011, the relative differences at the Frelighsburg site were positive and similar in magnitude to those at the Penn State site. For 2012–2019, the precipitation-weighted annual mean concentrations were 5–27% lower than NADP, except for H+, which was 23% higher. The change in sample collector by NADP had the largest effect on between-network biases. The comparisons of daily-vs-weekly measurements conducted by the CAPMoN network during 1999–2001 and 2016–2017 show that the weekly measurements were higher than the daily measurements by 1–3% for SO42−, NO3−, and NH4+; 3–9% for Ca2+, Mg2+, Na+, and Cl−; 10–24% for K+; and lower for H+ by 8–30% in terms of precipitation-weighted mean concentration. Thus, differences in sampling frequencies did not contribute to the systematically higher CAPMoN measurements. Understanding the biases in the data for these networks is important for interpretation of continental scale deposition models and transboundary comparison of wet deposition trends.Wet deposition monitoring is a critical part of the long-term monitoring of acid deposition, which aims to assess the ecological impact of anthropogenic emissions of SOThe online version contains supplementary material available at 10.1007/s10661-023-11771-z. Long-term and routine measurements of chemical components of precipitation are critical parts of the long-term monitoring of acid deposition, and have been carried out around the world, e.g., the European Monitoring and Evaluation Programme (EMEP) and the Acid Deposition Monitoring Network in East Asia (EANET) . NADP also operated the Atmospheric Integrated Research Monitoring Network (AIRMoN) during 1992–2019. Samples from the NTN are collected on a weekly basis, while samples from the AIRMoN were collected on a 24-h basis, starting from the onset of a precipitation event. The NADP samples are sent to the Central Analytical Laboratory (CAL), which was within the University of Illinois prior to 2018 and currently is at the Wisconsin State Laboratory of Hygiene (WSLH).The measurements of wet deposition by NADP go back as far as 1978 through the establishment of the National Trend Network (NTN). The NTN is the only network providing long-term measurements of chemical components in precipitation across the USA (The CAPMoN network has been operated by Environment and Climate Change Canada (ECCC) since 1983 . In order to assess the comparability of data from the two networks, collocated CAPMoN and NADP measurements have been made since 1986 at two sites, one in each country. The measurements were analyzed by Sirois et al.  was in a rural area of southwestern Quebec, 5 km from the Canada-US border . The instruments were situated on a grassy open field surrounded by mixed forest. In late 2001, the Sutton site was relocated by 15 km to Frelighsburg, Quebec . The Frelighsburg site is in a rural area with some agricultural land use, well away from influence of industrial and urban activities, as described by Wetherbee et al. , nitrate (NO3−), ammonium (NH4+), hydrogen ion (H+ from pH), calcium (Ca2+), magnesium (Mg2+), sodium (Na+), potassium (K+), and chloride (Cl−). Specific conductance is also measured by NADP. CAPMoN also analyzes samples for total nitrogen.CAPMoN and NADP samples are analyzed for nine major ions: sulfate . Flame atomic absorption spectrometry was used for Ca2+and Mg2+ until 2013, when they began to be analyzed by ICP-AES. Flow injection analysis (FIA) colorimetry is utilized for total nitrogen (TN) and NH4+, and electrometry for pH. Trace samples (<= 0.2 mm of precipitation depth) are not analyzed. Sample analysis is prioritized for analysis of anions first, followed by base cations, NH4+, pH, and TN. Non-trace samples with minimum pipette volume of 0.5 mL or 1 mL were diluted to 9 or 5 times dilution, respectively, enough for anion analysis only. Samples with enough volume for complete analytical analysis are also diluted when the samples look highly contaminated prior to analysis or when they are determined to be outside the calibration range. pH analysis is not performed on diluted samples. Data quality assurance and quality control are performed using the Research Data Management and Quality Assurance (RDMQ) system  is utilized for ClPrior to 2018, weekly composited NADP samples were collected in deionized water (DI)–cleaned, high-density polyethylene (HDPE) buckets and transferred to DI-cleaned, 1-L HDPE bottles for shipment to the NADP Central Analytical Laboratory (CAL) at the University of Illinois-Urbana/Champaign (UI). In 2018, the NADP and CAL moved from UI to the Wisconsin State Laboratory of Hygiene, University of Wisconsin-Madison (UW). The NADP transitioned to a bag-lined bucket sampling system in 2020, the data for which are from beyond the study period. N-CON Systems, Inc. Model ADS 00-120 (NCON) sample collectors replaced the Aerochem Metrics Model 301 (ACM) collectors in a subset of NADP sites since 2010 . Prior to 2016, samples were analyzed for pH and specific conductance upon receipt, then filtered for the remaining analyses. During the study period, anions were measured by IC, major cations by inductively coupled argon plasma optical emission spectrometry (ICPOES), ammonium by FIA, and electrometry for pH and specific conductance. At the start of the study period, pH and specific conductance were measured first, and then samples of trace quantity were diluted to suitable volumes for remaining analyses. This analytical priority changed in 2016, and the order became FIA > IC > ICPOES, and then pH > specific conductance if undiluted sample remained. In 2017, the CAL transitioned to a new IC method that uses a separation column and eluent that are both different from those used by the previous method.https://nadp.slh.wisc.edu/networks/national-trends-network/) or by request. The NADP data are internally quality assured  is the calculated Winsorized standard deviation.Modified median absolute deviation (MMAD)  different from zero in statistics, respectively.In computing MMAD, first the median of a list of values, which in this study is the difference of each paired CAPMoN-NADP weekly concentration, is found; secondly, this median is subtracted from each value of the list; finally, a new median is determined from the new list. A coefficient 1/0.6745 is applied to the new median so that the calculated MMAD is the same as the traditional standard deviation when the list of value follows a normal distribution.In comparing weekly concentration, both arithmetic mean and median value are calculated and presented in Tables 42−, NO3−, NH4+, and H+, the relative differences of the median ranged from 0.003 mg L−1 for H+ to 0.148 mg L−1 for NO3−. In units of microequivalents per liter (μeq L−1), it ranged from 1.37 μeq L−1 for SO42− to 3.02 μeq L−1 for H+. The relative differences were 3.7%, 8.8%, 16%, and 7.6% for SO42−, NO3−, NH4+, and H+, respectively. During the warm (cold) season, the corresponding relative differences were 1.9% (6.6%), 5.4% (12.8%), 13.6% (18.5%), and 5.6% (9.4%). The relative differences were smaller during the warm season than the cold season, especially for SO42−, NO3−, and H+. The relative standard deviations were between 24.0% for SO42−, and 35.1% for NH4+. The spread of the one-to-one scatter plots (not shown) is quantitatively described by the metrics of CoV. The CoV for each ion was much smaller than the relative standard deviation, ranging from 9.5% for SO42− to 18.3% for NH4+. The correlation coefficient was between 0.83 for NH4+ and 0.95 for SO42−. In general, there was a good correlation between CAPMoN and NADP for the weekly concentrations of SO42−, NO3−, NH4+, and H+. The correlation coefficients for the warm and cold seasons were comparable for SO42−, NO3−, and H+. However, the correlation coefficient for NH4+ was 0.92 for the cold season, higher than 0.76 for the warm season.The statistics for the Penn State site during 1986–2019 are shown in Table −, the median differences ranged from 0.002 mg L−1 for Na+ to 0.013 mg L−1 for Cl−. In units of μeq L−1, it ranged from 0.09 μeq L−1 for Na+ to 0.60 μeq L−1 for Ca2+. The relative differences were between 5.6% for Na+ and 21.1% for K+. The CoV was between 19.7% for Cl− and 44.9% for K+, indicating generally the one-to-one comparisons of weekly concentration were more scattered for base cations and Cl− than for SO42−, NO3−, NH4+ and H+. Except for K+, there was a strong correlation for the weekly concentration between CAPMoN and NADP for base cations and Cl−, with the correlation coefficient ranging from 0.84 to 0.91. For Ca2+, Cl−, and Na+, the correlation coefficients were higher during the warm season than the cold season. As shown in Table p-values were less than 0.05 for all ions indicating that the weekly concentrations from CAPMoN were statistically higher than those from NADP. Scatter plots of precipitation-weighted monthly mean concentrations, instead of weekly concentrations for better visualization, for the Penn State site are shown in Fig. 42− had the best agreement between the two networks. The spread of the one-to-one comparison for NO3−, NH4+, and H+ was small, but there was an obvious positive bias for each ion. The spread of the plot for K+ was largest among all ions, and the spreads for Ca2+, Mg2+, Cl−, and Na+ were comparable.For base cations and Cl42−; 5–10% for NO3−, H+, and Cl−; 10–16% for Ca2+, Mg2+, and NH4+; and 21% for K+. The correlation coefficients were greater than 0.9 for SO42−, NO3−, H+, and Cl−; between 0.8 and 0.9 for NH4+, Ca2+, Mg2+, and Na+; and less than 0.5 for K+. The between-network biases were statistically significant (p < 0.05) for all ions.Overall, the relative differences of the weekly concentrations between CAPMoN and NADP were less than 5% for SO42−, NO3−, NH4+, and H+ were lower during 2005–2019 than 1986–2019, due to emissions reductions of SO2 and NOx in the eastern US and Canada since 1990 , close to 10% for NO3− and H+, and between 10 and 17% for NH4+, Ca2+, Mg2+, K+, Na+, and Cl−. The correlation coefficients were generally lower during 2005–2019, and it was greater than 0.9 for H+ only. This could be due to the aging of the sample collectors, either CAPMoN or NADP collectors, or both. The between-network biases were statistically significant for all ions. The two networks agreed better during the warm season, with the average relative bias of 8.4% during the warm season  of weekly CAPMoN-vs-NADP concentrations was low for SO42−, NO3−, and NH4+, with CoV ranging from 11.5 to 18.2%. The spread was relatively high for H+, Ca2+, Cl−, Mg2+, and Na+, with CoV ranging from 27.0% for Na+ to 30.7% for Mg2+, and K+ had the highest spread with CoV of 49.4%. The biases between CAPMoN and NADP were not statistically significant for SO42−, Ca2+, Na+, and Cl−, but were statistically significant for other ions from the t-test (not shown). However, the biases were statistically significant from the Wilcoxon signed-rank test, as indicated by the p-values in Table 42−, NO3−, NH4+, and H+, with r of 0.93–0.96. For base cations and Cl−, r ranged from 0.75 to 0.85, except for K+ with r of 0.57. The correlation coefficients for the warm season were higher than the cold season (Table S.r = 0.94–0.98) except for K+.During 2002–2011, for all seasons, the relative differences were 3.0%, 6.3%, 9.3%, and 13.5% for SO42−, NO3−, H+, Ca2+, Cl−, and Na+, ranging from 3.0 to 9.3%; moderate for NH4+, Mg2+, and K+, from 13.3% for Mg2+ to 17.7% for K+.Overall, CAPMoN has higher weekly concentrations than NADP for 2002–2011 at Frelighsburg. The relative bias was small for SO+, of no difference for H+, and 20% higher for other ions. For the current inter-comparison of CAPMoN-vs-NADP, we found that the relative biases changed from positive values during 2002–2011 to negative values during 2012–2019 for all season and cold season except for H+ and K+  and positive bias for H+ (43.0%) were statistically significant. Comparing 2012–2019 to 2002–2011, the average correlation coefficient for all ions decreased from 0.91 to 0.75 during the warm season, and from 0.81 to 0.60 during the cold season.For 2012–2019, the NCON sampler was used as the NADP sample collector at Frelighsburg. The inter-comparisons of collocated measurements at 12 sites in the USA during 2009–2015 by Wetherbee  showed tp-value and tau, were used to identify if the trend was statistically significant and the strength of the trend. For SO42−, the relative bias before 1998 varied much more than after 1998. During 1986–1998, the relative bias ranged from −11.2% in 1993 to 12.0% in 1998, with a mean value of 1.8% and standard deviation of 6.9%. During 1999–2019, the relative differences of SO42− varied less (3.1 to 9.9%), with a mean value of 5.5% and a standard deviation of 2.1%. There was a moderate increasing trend in the relative bias during 1999–2019, mainly due to cold season biases during 2010–2019. The relative biases during the warm season for 1999–2019 were small, with a mean value of 2.8% ± 1.9% versus 9.6% ± 4.1% during the cold season. The trend of the relative bias of NO3− was not statistically significant with p = 0.99 for the cold season, p = 0.24 for the warm season, and p = 0.39 for all seasons. The mean and standard deviation annual relative biases for each season were 9.4% ± 3.2% , 3.4% ± 4.9% (warm), and 13.3% ± 4.9% (cold). The M-K test for the trend in the annual relative bias for NH4+ indicated no significant trends for 1986–2010 and 2011–2019. However, there was a clear decrease of the relative bias from 2008 to 2011. The mean relative bias values for 1986–2010 and 2011–2019 were 18.0% and 11.1%, respectively. Seasonally, there was a weak decreasing (p = 0.05) and a weak increasing trend (p = 0.09) of the relative bias for 1986–2010 and 2011–2019 during the cold seasons. The relative bias during the warm season (18.7%) was higher than the cold season (14.7%). The relative bias of H+ had a decreasing trend (p=0.02) for 1996–2005, an increasing trend (p=0.02) for 2005–2011, and no trend for 2011–2019 (p=0.9). The relative bias of H+ turned negative during 2004–2007 for all seasons, during 2004–2008 for the warm season, and was negative only in 2004 for the cold season. Overall, for the recent one to two decades, the measured weekly concentrations from CAPMoN were higher than NADP at Penn State for SO42− (5.5%) and NO3− (9.4%) during 1999–2019, and NH4+ (11.1%) during 2011–2019.Time series of relative bias for each year are shown in Fig. −, the relative biases had an increasing trend for Ca2+ and Mg2+ (p = 0.06–0.09), and a weak increasing trend for Cl− (p = 0.2) during 1986–1997. During 1998–2019, the trends were flat for Ca2+, Mg2+, and Cl−. There is a known bias in Na+ concentration data collected by NADP before 1998 due to sample contamination  lower than CAPMoN during 1986–1998. Relative biases were positive during all seasons for Ca2+, Mg2+, Cl−, and Na+ during 1998–2019, except for a few years for Ca2+ during the warm seasons, with the mean values for the relative bias varying from 10.5 to 16.0%, and the standard deviations from 4.2 to 5.5%. For 1998–2019, the mean relative bias during the warm season were 4.4–11.4% for Ca2+, Mg2+, Na+, and Cl−, much lower than the values of the cold season (16.3–25.0%). For K+, there was a decreasing trend in relative bias for 1986–1993, an increasing trend for 1993–1999, a decreasing trend for 1999–2005, and no trend for 2005–2019. The corresponding mean relative bias and standard deviation during 2005-2019 was 17.4% ± 5.1%.For base cations and Cl2+, Cl−, Mg2+, and Na+, and since 2005 for K+, the relative biases between CAPMoN and NADP were generally constant. The weekly concentrations measured by CAPMoN were 10.5 to 17.4% higher. The relative biases during the warm season were much lower than during the cold season.Overall, since 1998 for Ca42−, NO3−, and NH4+ were highly correlated to each other (R > 0.89) at the Frelighsburg site. The M-K test indicated no trends for SO42− and NO3−, and a weak decreasing trend for NH4+ during 2002–2011, which was prior to the precipitation sampler changed from the ACM collector to the NCON collector in October 2011. For 2012–2019, there was a decreasing trend in relative bias for NO3−, and there were no statistically significant trends for SO42− and NH4+. The relative biases have changed from generally positive to generally negative since the sampler was changed. During 2002–2011, the mean values of the relative biases were 4.0% (SO42−), 6.7% (NO3−), and 14.2% (NH4+), compared to −4.3% (SO42−), −4.0% (NO3−), and −4.0% (NH4+) during 2012–2019. For 2002–2019, the agreement between CAPMoN and NADP was very good during the warm season, with low relative biases of −2.3% (SO42−), −2.7% (NO3−), and −0.1% (NH4+). For the cold season, the relative biases were relatively larger: −10.5% (SO42−), −6.3% (NO3−), and −10.4% (NH4+). This indicates that when the new NCON collector was deployed at the Frelighsburg site, the previous positive biases changed to negative biases. The biases were relatively small for the warm season, but greater during the cold season. For H+, the trend of the relative bias was similar to that at Penn State: there was a decreasing trend for 2002–2005, and a significant (α=0.05) increasing trend for 2005–2019, especially during the warm season. However, during the cold season, there was no statistically significant (α=0.05) trend during 2008–2019.As shown in Fig. −, there were no statistically significant trends for Ca2+, Mg2+, and Cl− during 2002–2011 (p > 0.7) and for 2012–2019 (p > 0.3). For Na+, there was no trend in relative bias for 2002–2011, but there was a weak decreasing trend for 2012–2019. For K+, there was a decreasing trend in relative bias for 2002–2011, but then it was mostly constant for 2012–2019. Comparing the periods before and after the collector change , the mean values of the relative biases changed from positive (2002–2011) to negative (2012–2019) from 9.9 to −7.8% (Ca2+), 13.6 to −4.4% (Mg2+), 7.0 to −1.9% (Na+), and 4.4 to −1.9% (Cl−). For K+, the mean relative bias changed from 21.8 to 8.7%. However, during the warm season, only Ca2+ had a negative mean relative bias during 2012–2019 (−4.3%), and positive mean relative biases varied from 1.6 to 6.6% for Mg2+, K+, Na+, and Cl−. Overall, with the NCON collector, the agreement between CAPMoN and NADP for base cations and Cl− was much better than the previous ACM sampler during the warm season, but for the cold season, except for K+, the relative biases changed from positive values to negative values and the absolute values remained relatively large.For base cations and Cl42− had a good agreement between CAPMoN and NADP for both annual and seasonal precipitation-weighted mean concentrations, with relative biases ranging 2.1–3.8%, CoV ranging 3.5–8.3%, and r >= 0.98. The agreement was exceptionally good for the warm season after 2000. Data for NO3− and NH4+ indicated consistent positive biases over the 1986–2019 period, 11.8% and 15.6%, respectively. The relative bias was comparable between the warm and cold season for NH4+, but was much smaller during the warm season than the cold season for NO3−. The correlation coefficients were greater than 0.97 for NO3−, and around 0.90 for NH4+, for both warm and cold seasons. The CoV for NO3− was exceptionally small (5.3%) for the warm season, indicating the agreement between CAPMoN and NADP would be very good if the biases were eliminated. The statistical metrics in Tables + was good with respect to relative bias (6.2%), CoV (8.7%), and correlation (r=0.99). However, after examining the time series of annual and seasonal precipitation-weighted mean concentrations for H+  and the correlation coefficient (0.5).For base cations and Cl42− and 5.9% for H+, and ranged 13.5–19.0% for other ions . For base cations and Cl−, r ranged from 0.61 to 0.82. The relative biases for the cold season were higher than the warm season except for NH4+ and Mg2+, and the averages of the relative biases were 10.4% and 15.1% for the warm and cold seasons, respectively. The relative biases changed from positive values during 2002–2011 to negative values during 2012–2019 except for H+. During 2012–2019, the relative biases ranged from −5.5 to −3.9% for SO42−, NO3−, and NH4+ . There was no statistically significant bias between CAPMoN and NADP except for H+ during the warm season of 2012–2019. During the cold season of 2012–2019, excluding H+ and K+, the relative biases were −19.2 to −7.4% with an average of −14.1% , the mean correlation coefficient reduced to 0.44 during the cold season, comparing to 0.95 during the warm season. These results indicate that, with the implementation of the NCON collectors by NADP, the agreement between CAPMoN and NADP improved significantly during the warm season, but during the cold season, relatively large biases existed.For Frelighsburg, separate statistical analyses were done for 2002–2011 and 2012–2019 due to the change of the NADP sample collector. The summary of statistical analysis is presented in Tables ns Table . The CoVH+ r = 0.8–0.99. F42− (5.1%), NO3− (14.9%), NH4+ (17.2%), and H+ (8.8%) (Table S.R >= 0.95) for SO42−, NO3−, NH4+, and H+. For base cations and Cl−, annual depositions estimated from CAPMoN data were 12.4–17.1% higher than from NADP data. The corresponding correlations were high for Ca2+ and Cl− (r = 0.96), relatively high for Mg2+ (r = 0.91), and moderate for Na+ and K+ . As expected, since the deposition depends on both the precipitation-weighted mean annual concentrations and the precipitation depth, both of which had positive median biases (Tables + (10.4%) and NH4+ (14.4%). During the cold season, the relative biases of the annual deposition were 8.0% for SO42−, 14.0% for H+, and 16.7–30.8% for other ions. During 2005–2019, the relative biases were 8.4% for SO42−, and 14.0–22.3% for other ions. The means of the relative biases of all ions during the warm season (10.2%) were smaller than during the cold season (21.0%)  and cold (13.9%) seasons. Strong correlation of annual depositions were indicated for all ions during the warm season (r= 0.96–1.0), except for slightly weaker for K+ (r=0.84). Overall during 2012–2019, except for H+ and K+, the agreement of annual deposition estimates from CAPMoN and NADP were very good during the warm season, but there were negative biases during the cold season.The annual depositions estimated from CAPMoN data were higher than from NADP data during 2002–2011 for all ions with a range of 11.1 to 23.0% Table S.g. The wa42−, NO3−, and NH4+. Relatively larger differences occurred for higher weekly concentrations for all ions. These higher weekly concentrations were usually associated with relatively lower weekly precipitation amounts . Table +, the weekly concentrations from the weekly measurements were higher than those from the daily measurements. Mean daily-minus-weekly concentration differences between the two sampling protocols were approximately −0.2 μeq L−1 for Mg2+, K+, Na+, Cl−; −0.4 to −0.8 μeq L−1 for NO3−, Ca2+, and NH4+; and −1.0 μeq L−1 for SO42−. The relative differences in precipitation-weighted concentration ranged from −1.2 to −3.1% for SO42−, NO3−, and NH4+; −4.2 to −7.2% for Ca2+, Mg2+, Na+, and Cl−; and −24.4% for K+. For H+, the weekly measurements underestimated the precipitation-weighted mean concentration by 2.5 μeq L−1, or 8.2%. The measurements from EW1 had relatively large biases, compared to the measurements from EW2, EG1, and EG2. If we only look at the relative differences between EW2 and EG1 or EG2, the weekly measurements overestimate SO42−, NO3−, and NH4+ by 1–2%; Ca2+, Mg2+, Na+, and Cl− by 3–5%; and K+ by 14%.From the spring of 1999 to the spring of 2001, a field study was carried out at Egbert, Ontario, Canada, by the CAPMoN network. Four identical CAPMoN precipitation collectors were deployed at the site to measure wet deposition of the common CAPMoN and NADP ions. Two samplers were operated to collect daily samples (coded as EG1 and EG2) and the other two collected weekly samples (coded as EW1 and EW2). The main objective of the study was to assess the comparability of the daily and weekly sampling. For this analysis, weekly precipitation-weighted mean concentrations were calculated from the daily sample data  for comparison to the corresponding weekly sample concentrations (coded as EW1 and EW2), analogous to the NADP comparison methodology. From the weekly concentrations, precipitation-weighted mean concentration was calculated for the entire study period 1999–2001, using the equation similar to Eq. 2+ had a relative difference greater than 1%. For EW1-vs-EW2 comparisons, only K+ had a relative difference greater than 1%. Using median value as a metrics, the weekly measurements showed 1–3% higher SO42−, NO3−, and NH4+ concentrations; Ca2+, Mg2+, Na+, and Cl− by 1–5%; and K+ by 6% compared to weekly composite values derived with daily measurements. Only H+ was higher in the daily composites, by 5%. Daily-vs-daily and weekly-vs-weekly comparisons are usually mentioned as “within-method” comparison, while daily-vs-weekly comparisons are named as “between-method” comparison. The results in Table S.Table S.+. Very good agreements of weekly concentration were found for SO42−, NO3−, and NH4+ between daily and weekly sampling. Tables +, and an increase in the precipitation-weighted mean concentrations for other ions. The effect on the precipitation-weighted mean concentration of H+ was −1.3 μeq L−1, or −30%, on average, while the effect on SO42−, NO3−, and NH4+ was less than 0.3 μeq L−1, or 3%. The effect on Ca2+ and Mg2+ ranged 0.3–0.6 μeq L−1, or 5–10%; the impact on Na+ and Cl− was approximately 0.2 μeq L−1, or 2%, and the impact on K+ was smallest in absolute value, being 0.1 μeq L−1, but 10.3% in relative difference as the mean concentration of K+ was the lowest among all ions.To aid the CAPMoN network in the transition of CAPMoN measurements of wet deposition at some sites from a daily basis to a weekly basis, parallel measurements with daily and weekly sampling frequencies were carried out by the CAPMoN network during 2016–2017 at Egbert and Algoma sites in Ontario, Canada, and at the Jackson site in Nova Scotia, Canada. Two types of sample collectors, C300 and D400, were deployed at Egbert. Only C300 samplers were deployed at Algoma and Jackson. As shown in the scatter plots  sites were not due to the difference in sampling frequency between the two networks, because CAPMoN weekly composite measurements from daily data were lower than the CAPMoN weekly measurements except for H+. Inter-comparisons of wet deposition measurements with different sampling periods, namely, weekly-vs-event, have been conducted in previous studies  and summer months (June–August) of the 1999–2001 and 2016–2017 data. The relative biases, expressed as daily-minus-weekly, of the precipitation-weighted mean concentration of H+ were reduced from 8.2% for the summer season to 1.1% for the winter season for 1999–2001 data. For the 2016–2017 data, the relative biases were reduced from 61% (for C300 samplers) and 79% (for D400 samplers) for the summer season to 23% (C300) and 21% (D400) at the Egbert site. For the Jackson site, it was reduced from 30 to 7.9%. No seasonal analysis was performed for the Algoma site due to limited data. Examples of scatter plots of weekly concentrations of H+ from daily samples vs. weekly samples are shown in Fig. + in precipitation samples when the overall acidity of precipitation decreased during the past three decades in eastern North America, which could account for larger discrepancies in the 2016-17 studies than in 1999-2001.Significantly lower concentrations of Ha et al.  and Sista et al. . It has a et al. . To test3−, NH4+, and H+.A number of potential causes for the observed between-network biases were proposed in Sirois et al. : (1) CAPWetherbee et al.  examined+, possibly due to a small amount of evaporation over the sampling week. However, the impact was only 1–3% for SO42−, NO3−, and NH4+, and it was in the opposite direction of the between-network biases. Additionally, Wetherbee and Rhodes  could be mainly due to the differences in sample collector performance for the two networks.The change of the comparability of sample depth between CAPMoN and NADP was consistent with the change of the between-network biases from positive to negative for most ions except for H+, measured by CAPMoN were higher than those from NADP when the ACM was deployed at the Penn State and Frelighsburg sites. With the NCON being deployed at Frelighsburg during 2012–2019, the sample depths from NADP and CAPMoN became comparable, and the overall between-network biases turned negative (except for H+ and K+). The between-network bias for H+ continued to be positive at Frelighsburg during 2012–2019. This is consistent with the results of the CAPMoN daily-vs-weekly inter-comparisons, which showed that the concentrations of H+ in weekly samples were substantially lower than daily samples. Biological uptakes/conversion and particle dissolution might have reduced the concentrations of H+ in weekly samples  for inter-network biases are laid out in the World Meteorological Organization Global Atmosphere Watch Manual for the Precipitation Chemistry Programme WMO, . The MMAWet deposition data from NADP and CAPMoN have been jointly used for evaluating global and regional models , NO3− (12%), NH4+ (16%), H+ (6%), and base cations and Cl− (11–15%). For annual deposition, CAPMoN was 5–17% higher for all ions, with the best agreement for SO42−.At the Penn State site, for the whole study period 1986–2019, CAPMoN was higher than NADP for all ions, in terms of weekly concentration, precipitation-weighted annual mean concentration, and annual deposition. The precipitation-weighted annual mean concentrations were higher for SO+, which was 23% higher; the NADP-measured precipitation amount was 3.6% higher. Correspondingly, the annual deposition from CAPMoN was 3–15% lower than NADP, except that the H+ deposition was 30% higher. This study further confirms that the implementation of a new type of sample collector introduced systematic and notable changes in measured concentrations and deposition within the NADP network, as indicated in the previous study by Wetherbee  and 14–23% (NH4+) higher than NADP when precipitation samples were collected by the ACM collector. However, when the NCON collector was deployed at the Frelighsburg site, the annual deposition of nitrogen by CAPMoN was 5% and 3% lower than NADP for NO3− and NH4+, respectively. This study shows that between-network differences and within-network differences  create biases in the data that need to be considered when assessing the impact on ecosystems from atmospheric deposition .The inter-comparison results at Penn State and Frelighsburg (for 2002–2011) show that the deposition of nitrogen measured by CAPMoN was 15–18% .In this study, we compared the weekly concentrations of nine major ions measured by NADP and CAPMoN at two sites located in the Penn State, USA, and Frelighsburg, Canada, for the periods of 1986–2019 and 2001–2019 respectively. The major findings from this inter-comparison study are summarized as follows:ESM 1(DOCX 312 kb)


The standard quality, respiration rate, postharvest aptitude, sensory quality, phenols, and antioxidant systems (non-enzymatic and enzymatic) were analysed at 14 and 21 days of storage. Postharvest treatment with melatonin 0.5 mmol L−1 improved firmness and reduced weight loss and non-commercial fruit percentage while increasing respiration rate, lipophilic antioxidant activity, and ascorbate peroxidase enzyme activity. Furthermore, the treated cherries showed better sensory qualities, such as uniformity of colour and skin colour, as well as being sourer and showing better consumer acceptance and liking after 14 days of storage. Therefore, we conclude that the 0.5 mmol L−1 concentration is effective on the standard, sensory, and bioactive quality of early sweet cherries and can be considered an eco-friendly tool for maintaining the postharvest quality of early cherries.Melatonin (N-acetyl-5-methoxytryptamine) is involved in multiple functions in plants. However, its role in some metabolic pathways and exogenous application’s effect on fruits is still unclear. Furthermore, the effects of pre-storage melatonin treatment on sensory traits and consumer acceptance of cherries have yet to be studied. For this reason, the early sweet cherry cultivar ‘Samba’ harvested at the commercial ripening stage was treated with different melatonin concentrations (0.1, 0.3, and 0.5 mmol L Prunus avium L.) is known to be a fruit highly appreciated in markets by consumers, not only for its organoleptic characteristics but also for its high antioxidant activity due to bioactive compounds, such as flavonoids, vitamins, and carotenoids [Turkey is the leading producer of cherry production, while Spain ranks sixth . Spain eotenoids ,4,5. Howotenoids . Its higotenoids .2 generated during storage in these bags is not enough to guarantee adequate quality at a long destination point [The high economic and nutritional value of cherries has encouraged many researchers to study their physiological and molecular basis of postharvest behaviour, particularly its impact on quality traits ,8. Posthon point . For thion point , methyl on point , acetylson point  and β-amon point  that woron point , delayinOn the other hand, many researchers have focused their studies on using melatonin (M) for its bioregulatory activity in plant physiological processes such as growth and development regulation, senescence delay and fruit ripening regulation. Melatonin (N-acetyl-5-methoxytryptamine) is a derivative of the amino acid tryptophan and was first identified in plants in 1995 . In addiPrevious studies on postharvest melatonin dipping treatment in sweet cherries have been carried out by means of using applications at concentrations between 1 and 1000 µM at different temperatures, such as 5 and 20 °C, with a duration of 5 min ,5,7,21. −1 (M0.1), 0.3 mmol L−1 (M0.3) and 0.5 mmol L−1 (M0.5). Hydrocooling treatment was applied until reaching a pulp temperature below 8 °C. Each batch was dipped in the different melatonin solutions  and CO in water for 10 min at 5.6 ± 0.5 °C and dried at room temperature for approximately 30 min. Subsequently, cherries were stored in 250 g macroperforated punnets at 1 ± 0.5 °C and 93.8 ± 2.7% relative humidity (RH) and analysed at 0, 14 and 21 days after a 4 h post-cooling period at room temperature (20 °C). All analyses were performed in triplicate and were shown as mean values ± standard error (SE).The study was carried out with sweet cherries obtained from a commercial orchard of 25 eight-year-old trees of the early ‘Samba’ cultivar planted at 5 × 5 m and grafted onto Mariana-Adara rootstock, located in Jerte Valley . Trees were subjected to standard fertiliser, herbicide, and pesticide practices. This early cultivar is firm and has a medium-sized stem, heart shape, dark red skin, and pale red flesh . Sweet c−1, and the maximum force (N) was recorded from the force-deformation (N mm−1) curve. Skin and flesh colour were measured with a CR-4OO reflectance colourimeter  with a D65 illuminant and an 8 mm diameter viewing area; CIELab space coordinates were recorded of 10 independent fruits for each replicate on four opposite sites around the equator for the skin and the two opposite sites for the flesh. The result was expressed as L* (luminosity) and a*/b* index, related to the fruit ripening stage [Firmness was analysed by a 3% compression test on two opposite positions around the equator of 10 independent fruit for each replicate using a 25 mm flat base probe. A Stable Micro Systems TAXT2i texturometer  was used. The displacement speed of the test was 0.2 mm sng stage . With chn = 3). Results were expressed as mg CO2 kg−1 s−1. The respiration rate of whole sweet cherries was evaluated by a static system  using a n = 3), and calculated in percentage [Weight loss was measured at each sampling point, compared with an initial weight of 250 g of sweet cherries  conducted the sensory analysis on the 3 sampling points , tasting 3 cherries each panellist per treatment  after keeping them for 4 h at room temperature. Sensory properties related to appearance, colour, firmness, sweetness, sourness and other sensations were trained during 5 sessions. Informed consent was obtained from the panellists. Samples were randomly presented using three-digit reference codes. The sensory descriptors used were external appearance, colour uniformity, skin colour, sourness, sweetness, crispness, and firmness. A ten-point scale was used to judge the proposed descriptors. The sensory analysis was carried out in 12 individual standardised , using wA panel of fifty consumers  who were regular consumers of cherries randomly assessed 3 cherries from each treatment on each sampling date, also using a three-digit reference code and were asked to score their degree of disliking/liking using a nine-point hedonic scale  for consumer satisfaction. After, consumers were asked about their purchase intention, answering yes or no based on all the sensory parameters previously evaluated.n = 3) from the different treatments were carried out to identify and quantify the bioactive compounds. At each sampling point, 15 fruit per treatment and replicate were frozen at −80°C. Independent homogenisations of 15 fruits (−1 of fresh weight (FW).Phenolic compounds were extracted as described in our previous work by Serradilla et al. . Brieflyg for 30 min at 4 °C. The upper (lipophilic) phase was used to determine L-TAA and the lower (hydrophilic) phase for H-TAA. In both cases, TAA was determined using the enzymatic system consisting of ABTS, the enzyme peroxidase and its substrate (hydrogen peroxide). Results were expressed as g Trolox equivalent Kg−1 of fresh weight (FW). Total antioxidant activity (TAA), both hydrophilic and lipophilic fractions (H-TAA and L-TAA), was measured according to Serrano et al. . For eacp/v) polyvinylpyrrolidone and 1 mM ethylenediaminetetraacetic acid. It was centrifuged at 21,100× g for 30 min at 4 °C, and the supernatant was used for enzyme assays. Results were expressed as U min−1 g protein−1, with one enzymatic unit (U) being a 0.01 absorbance increase per min.The activity of the enzymes peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX) was measured as described by Carrión-Antoli et al. . Brieflyp-value ≤ 0.05. Multiple comparisons test was carried out using Tukey’s HSD post hoc test. Experimental data were subjected to one-way and two-way ANOVA analysis using SPSS Statistics 25.0  software for Windows. The significant effect of treatment and storage time on the variables under study was evaluated at a −1  was 1.50 ± 0.03 N mm−1 . p ≤ 0.05) in firmness during cold storage, reaching maximum firmness values after 14 days of cold storage for all treatments (p ≤ 0.05) with untreated cherries (1.91 ± 0.04 N/mm) after 14 days.On the one hand, treated and untreated ‘Samba’ cultivar cherries exhibited a significant increase  among sampling points, but no differences were observed among treatments at the same sampling point. However, after 21 days of cold storage, TSS content was significantly lower than at harvest and 14 days (p ≤ 0.05) at 14 and 21 days, reaching 0.63 ± 0.01% malic acid after 21 days of storage.L* skin values ranged from 28.24 ± 0.11 at harvest to 29.98 ± 0.12 after 21 days of storage, while flesh a/b ratio ranged from 1.83 ± 0.03 (Day 0) to 2.03 ± 0.02 after 21 days of storage. It is also remarkable that flesh a/b was the only colour parameter that showed a significant interaction between sampling day and treatment . TSS con 14 days . In this2 kg−1 s−1, while during cold storage, significant differences (p ≤ 0.05) were observed between CO and M0.1 with M0.3 and M0.5, the latter two treatments showing the highest respiration rates and a significant increase after 14 and 21 days of cold storage (The respiration rate at the time of harvest was 0.01 ± 0.00 mg CO storage . p ≤ 0.05) with M0.1 and CO.Weight loss increased throughout storage, with CO and M0.1 showing a significant steady weight loss, with 0.30 ± 0.17% and 0.42 ± 0.05% at 14 days and 0.66 ± 0.04% and 0.77 ± 0.04% at 21 days of storage, respectively a. After Concerning stem browning, its severity remained at grade 1 up to 21 days of storage, and there were no significant differences for this disorder. However, there was a high percentage of pitting  during cold storage b, ranginp ≤ 0.05) were observed in all sensory attributes tested, except crispness and firmness. The external appearance was very similar for all treatments, scoring very high (8.6) at the beginning and significantly lower at 14 and 21 days of storage . Colour uniformity was generally fairly stable throughout cold storage, with significant differences (p ≤ 0.05) among treatments at 14 days, with M0.3 and M0.5 treatments showing significantly higher values than untreated cherries (Significant differences (cherries .p ≤ 0.05) were observed among treatments, with M0.1 treated fruit showing a lower skin colour than M0.3  to 10 (black). All cherries showed a mahogany colour (7.2) at the beginning of the trial. The colour remained fairly stable throughout storage in all treatments, except for M0.3 cherries, which acquired a darker colour (8.4) at the end of the trial. At 21 days, in addition, significant differences (han M0.3 . p ≤ 0.05) were only found at 14 days of storage, with M0.5 samples showing significantly higher values than CO  according to the training previously carried out for this attribute. A significant decrease in sourness was observed after 14 days of cold storage in CO and M0.3 treatments, remaining stable in M0.1 and M0.5 cherries. By treatments, significant differences ( than CO . At the p ≤ 0.05) were only found at 14 days of storage, with M0.1 significantly lower than CO.The sweetness was, overall, fairly stable throughout storage at 2 °C , with ‘SThe degree of disliking/liking was evaluated using a nine-point hedonic scale. Although no significant differences were found either among treatments or among sampling points, an evolution in consumer satisfaction with cherries was observed . The iniPurchase intention represents the percentage of consumers who, after tasting the fruit, answered that they would repurchase it. According to this parameter, no significant differences were found either among treatments or sampling dates. Nevertheless, the purchase intention evolved positively from day 0 (72.7%) to day 14 (85.4%), decreasing after 21 days of storage at 64.2%. By treatments, at 14 days, all melatonin treatments received a higher purchase intention than CO (75%), especially M0.5 (91.7%) and M0.3 (91.7%). Finally, after 21 days of cold storage, purchase intention drops to 75% for M0.5, 66.7% for M0.3, 65% for CO and 50% for M0.1.The phenolic compounds identified and quantified in the early Samba cultivar were grouped into anthocyanins, hydroxycinnamic acids, flavonols and flavan-3-ols .O-rutinoside, showed significant differences (p ≤ 0.05) between treated and untreated cherries. Melatonin-treated cherries maintained higher concentrations of this compound throughout storage and, with it, a better skin colour. On the other hand, significant differences (p ≤ 0.05) were also found in the total sum of anthocyanins, with cherries treated with melatonin showing the highest concentration. It should be noted that a strong interaction (p ≤ 0.001) was observed between the two study factors, storage time and treatment on the total anthocyanin concentration  with untreated cherries in the case of neochlorogenic acid. As with anthocyanins, the total sum of hydroxycinnamic acids was significantly influenced (p ≤ 0.05) by the interaction of treatment and storage time, showing a positive effect of postharvest treatment with melatonin on this group of polyphenols.Another group of phenolics of high importance in cherries are the hydroxycinnamic acids, especially the neochlorogenic acid and p ≤ 0.05) were only found between cherries treated with M0.3 and untreated cherries in the concentration of kaempherol 3-O-rutinoside.In the case of flavonols, significant differences (p ≤ 0.05) were found between M0.5 melatonin-treated and untreated cherries for the concentration of procyanidin PB2, (+)-Catechin and (−)-epicatechin. In general, postharvest treatment with melatonin had a positive effect in delaying the loss of polyphenols, except flavonols, throughout the storage process and, thus, preserving the bioactive characteristics of this fruit. Regarding flavan-3-ols, significant differences (−1 of FW at 0 days and 0.83 ± 0.07 and 0.82 ± 0.09 (g Kg−1) at 14 and 21 days of cold storage, respectively (p ≤ 0.05) throughout cold storage. However, M0.3 and M0.5 treated cherries showed a better H-TAA than CO, highlighting that M0.5 treated cherries showed an H-TAA level more like day 0. By contrast, melatonin treatments induced a sharp increase of 33.62% (M0.1), 72.67% (M0.3), and 72.45% (M0.5) in lipophilic total antioxidant activity (L-TAA) at 21 days of storage compared to day 0 and untreated cherries  was not influenced by pre-storage melatonin application a. The meectively a. In thecherries b.−1 g protein−1). Because of that, there were no significant differences between treated and untreated cherries, although it was observed that M0.3 treated cherries showed the highest activity for this antioxidant enzyme after 21 days of storage. With regard to CAT (−1 g protein−1) after 14 days of cold storage and significant differences (p ≤ 0.05) compared to both other treatments and CO that showed a mean value of 289.11 ± 10.71 U min−1 g protein−1. A growing trend was observed in APX activity during the first 14 days of postharvest storage (The activity of antioxidant enzymes peroxidase (POD), catalase (CAT) and ascorbate peroxides (APX) was measured throughout cold storage. The antioxidant enzyme POD showed steady activity throughout storage a, showind to CAT b, it was storage c. HoweveIn recent literature, there are several works on the effect of postharvest melatonin dipping in sweet cherries, where melatonin is not only a safe and non-toxic substance for humans but also an important signalling molecule that functions as a master regulator of certain physiological traits and antioxidant systems of fruits, delaying postharvest diseases and senescence process in sweet cherries ,21,33,34Sweet cherry quality is evaluated through its physicochemical parameters and evolution throughout its commercial life or shelf life. Losses in weight, firmness and titratable acidity during storage and subsequent shipment, along with changes in skin colour and total soluble solids content, define their quality and consumer acceptance as well as their repurchase . Once hap ≤ 0.05) only at M0.5  in TSS and TA throughout storage (Fruit flavour and consumer acceptance are closely related to TSS and TA parameters ,43. Acco storage . It shouOn the other hand, in this study, trained panellists found differences in sweetness and sourness after 14 days of storage , with meAmong the parameters that most influence the decision to purchase cherries is colour . In addi-+ radical scavenging potential and suppression of endogenous H2O2 accumulation [During this study, it was found that melatonin enhances the enzymatic and non-enzymatic antioxidant systems of the ‘Samba’ sweet cherry. These results agree with other authors’ results in sweet cherry ,21,32,34mulation . Differemulation ,21,34 remulation . It was Regarding enzymatic antioxidant activity, melatonin postharvest application to the cultivar ‘Samba’ increased POD and CAT activity at day 14 and APX activity at 21 with respect to the control fruit . This le−1, by immersion, maintained the enzymatic and non-enzymatic antioxidant systems of ‘Samba’ sweet cherry during storage, providing firmer cherries without negatively altering skin colour and flavour, leading to improved organoleptic characteristics as well as better purchase intention after 14 days of storage. Therefore, applying melatonin before storage can be considered an excellent postharvest tool to maintain the standard, sensory, and bioactive quality of early cherries. However, more studies are needed to clarify the mechanism of action of melatonin.Pre-storage application of melatonin, especially 0.5 mmol L


Cardiovascular disease is a cluster of illnesses that affect the heart and blood vessels. Dyslipidemia is the most common risk factor for cardiovascular disease, causing more than 4 million deaths each year worldwide. However, there is very little evidence concerning the prevalence and pattern of dyslipidemia among cardiac patients in Ethiopia.Hospital-based cross-sectional study was conducted from June to September 2022 at Ambo University referral hospital. Data on socio-demographic, clinical and anthropometric features were collected from adults with cardiac diseases using a convenient sampling technique. Lipid profiles and uric acid were measured from overnight fasting blood. The national cholesterol education program adult treatment panel (NCEP-ATP) III criteria was used to define dyslipidemia.A total of 269 participants were enrolled and the overall 76.6% [95% confidence interval (CI):72.1–81] of patients had at least one dyslipidemia. The prevalence of total cholesterol (TC) ⩾200 mg/dl, triglyceride (TG), LDL-cholesterol and HDL-cholesterol < 40 mg/dl were 38.9%, 44.6%, 29.4%, and 53.5%, respectively. Age > 54 was associated with TC and TG dyslipidemia, adjusted odds ratio (aOR) and (95% CI) were 2.6(1.4–4.8) and 2.4(1.2–4.7), respectively. While, a family history of heart disease, sedentary lifestyle and obesity were associated with TC dyslipidemia, aOR (95%CI) were 1.9(1.1–3.5), 1.4 (1.4–14.6) and 6.7 (1.4–32.5), respectively. In addition, diabetetes mellitus and abdominal obesity were significantly associated with TG dyslipidemia, aOR (95%CI) were 1.9(1.0–3.6) and 2.6(1.16–5.8), respectively. Moreover, uric acid was positively correlated with TC and TG level.The results indicate that more than 75% of the cardiac patients had at least one dyslipidemia. This reflects the need for regular monitoring of lipid profiles and intensive counseling in this population to mitigate further cardio-metabolic complications. Cardiovascular diseases(CVDs) are a group of disorders that damage the cardiovascular system such as heart, blood vessels, and circulatory system , 2. Due Dyslipidemia is the most important modifiable risk factor of the cardiovascular disease. It can be defined as an increasing concentration of lipids and lipoproteins in the blood, either individually or in combination , 8. LipiHypertriglyceridemia combined with high LDL-c significantly increases the risk of coronary artery disease (CAD). World health organization (WHO) estimates of 2012 showed that dyslipidemia accounted for 18% of ischemic heart disease, 56% of stroke, and more than 4 million deaths per year globally . A populThe burden of dyslipidemia can vary from person to person and geographical location depending on age, disease, and environment, dietary and lifestyle-related factors. The frequent bunching of dyslipidemia and other CVD risk factors in cardiac patients has been shown to act synergistically, accelerating the development of atherosclerosis and cardiovascular morbidity and mortality. Identifying the potential contributory factors of dyslipidemia in CVD patients is crucial in order to manage the disease condition and reduce further complications. Therefore, this study aimed to fill this gap by assessing the prevalence, pattern, and associated factors of dyslipidemia among patients with CVDs.The study was conducted at Ambo university referral hospital (AURH) in west Ethiopia. AURH was established in 2016 and situated in Ambo town which is the capital of the west Shewa zone, 114 km away from Addis Ababa . A hospital-based cross-sectional study was conducted among adult patients with cardiac disease. Adults who had cardiac problems with age ≥ 18 years old were eligible for the study. However, patients using lipid-altering drugs, women with confirmed pregnancy, previously diagnosed HIV patients and receiving antiretroviral agents, patients with serious illness, and patients with known chronic liver and renal failures were all excluded from the study.P = proportion of dyslipidemia, Zα/2 = critical value at 95%, level of confidence (Z = 1.96), d = margin of error (5%), n = the required sample size, which is 358. However, the number of source populations is < 10,000; sample size correction was performed using Cochran's formula for sample size correction. A final sample size of 269 was then calculated. Finally, a consecutive convenient sampling technique was applied to select and include the study participants.The sample size was estimated using single population proportion formula considering 63% of dyslipidemia in CAD patients  with a 92) and the results were recorded. Then BMI was categorized as underweight (BMI < 18.5 kg/m2); normal weight (BMI = 18.5 to 24.9 kg/m2); overweight (BMI = 25 to 29.9 kg/m2); and obese  and waist circumference were taken by trained professional nurses working at the chronic diseases clinic, based on the WHO step-by-step approach to surveillance of non-communicable disease risk factors . The hei30 kg/m2 .While the waist circumference (WC), on the other hand, was measured at the midpoint between the iliac crest and the lower rib with non-elastic measuring tape. Blood pressure was measured with a mercury sphygmomanometer (UM-211 blood pressure monitor) and the accuracy of the measurement was maintained by measuring at least two readings within 3–5 min of difference after patients resting in the clinic for a minimum of 10–15 min and finally the mean blood pressure (BP) was recorded. Moreover, the global physical activity questionnaire of the STEPS instrument was used to assess physical activity status . automated clinical chemistry analyzer was used to determine lipid profile and uric acid from serum sample. The enzymatic colorimetric assay method was used to determine total cholesterol using cholesterol oxidase, phenol 4-amino antipyrine, and peroxidase (CHOD-PAP) reagents; and triglyceride using glycerol phosphatase, phenol 4-antipyrine and peroxidase(GPO-PAP) regents. In addition, LDL-c was measured using cholesterol reaction along with reagents that block the contribution of HDL-c and very low density lipoprotein (VLDL), while the HDL-c was measured by a homogenous enzymatic colorimetric method that used polyanions and a detergent that blocks non-HDL-c lipoproteins. Uric acid was measured by enzymatic colorimetric test in which the uricase enzyme cleaves uric acid to form allantoin and hydrogen peroxide. In the presence of peroxidase, 4-aminoantipyrine is oxidized by hydrogen peroxide to a quinone-diimine dye. Then the color intensity of the quinoneimine formed is directly proportional to the uric acid concentration.A 4–5 ml of venous blood sample was collected from each subject after overnight fasting and COBAS-311Dyslipidemia: was defined according to national cholesterol education program adult panel III (NCEP-ATP III) guidelines, cut-off points that place an individual at risk for cardiovascular disease is: TC ≥ 200 mg/dl, HDL-c < 40 mg/dl, LDL-c ≥ 130 mg/dl and TG ≥ 150 mg/dl [50 mg/dl , whereas50 mg/dl .Abdominal obesity: men with a WC ≥ 102 cm or women with a WC ≥ 88 cm [ ≥ 88 cm .Low fruit/ vegetable intake: was defined as Intake of seven-day history was used and < 4-day use of fruit and vegetables in a week [n a week .p-value < 0.25 in bivariate analysis was considered for multivariable analysis and finally a p-value < 5% was accepted as statistical significance.The data from each questionnaire were checked visually and entered into Epi-Data version 4.6 . And then exported and analyzed using the Statistical Package for Social Science (SPSS), version 25. Descriptive statistics such as frequency and percentages were applied to summarize categorical variables. While means and standard deviation also was used for continous data. The chi-square test was used to evaluate the significance of categorical variables with the study outcome; while Pearson’s correlation coefficient was used to find out correlations between the lipid profiles and different independent variables. Both bivariate and multivariable binary logistic regression models were used to evaluate the association of independent factors with outcome variables. Moreover, only a variable with a The quality of data was maintained by pre-testing of 10% questionnaires at Meti Health Center prior to actual data collection and then all required amendment was done on questionnaires following a pre-test feedback. Appropriate guidance was given to the data collectors by the principal investigator on how to collect all relevant data for the study purpose. In addition, all laboratory procedures were performed strictly in accordance with the standard operating procedures. The proper functioning of instruments, laboratory reagents and technical performance were checked daily through performing quality control.A total of 269 adults with known cardiac disease were included in the study. Of all the study participants, 153(56.9%) were males. The mean age (± SD) of the study subjects was 51.13 ± (15.83) ranging from 18 to 89 years. One hundred sixty-three (60.6%) of the study participants were urban dwellers. The majority (141 = 52.4%) of the study participants had an educational status above secondary school, while 59(21.9%) were unable to read and write. Concerning occupation, ethnicity and marital status; the majority 76(28.3%), 189(70.3%), and 164(61%) were farmers, Oromo and married, respectively.Forty-six 17%) and 59(21.9%) of the study participants had a history of smoking and alcohol consumption, respectively. In addition, 18 (6.7%) and 28(10.4%) were currently smoking and drinking alcohol, respectively. One hundred ninety (70.6%) of the study participants had less active to sedentary lifestyles. Moreover, one hundred sixty-two (60.2%) of the study participants had low fruit/vegetable consumption habit (Table 7% and 59The mean (± SD) of SBP, DBP, BMI, and WC of the study participants were 132.83 ± 14.9, 85.5 ± 7.4, 24.39 ± 4.02, and 91.42 ± 10.4, respectively. More than half (140 = 52%) of the study participants had normal weight, 68(25.3%) were overweight, 43(16%) were obese and the remaining 18(6.7%) were underweight. In addition, 148(55%), 77(28.6), and 106(39%) of study participants had a history of hypertension, DM and a family history of cardiovascular disease (FHHD), respectively. The mean (± SD) of participants’ time since heart disease and treatment experience were 3.88 ± 2.134 and 3.23 ± 1.8 years, respectively.p = 0.59), while LDL-c dyslipidemia was marginally higher in females than males (34.5% vs. 25.5% p = 0.11), respectively. In addition, participants aged > 54 years had significantly higher TC  and TG  than participants aged ≤ 54 years. The prevalence of TC, TG, and LDL-c-dyslipidemia was significantly higher in participants with abdominal obesity than participants with normal WC. Moreover, TC, TG, and LDL-c dyslipidemia were higher in participants with a sedentary lifestyle, while HDL-c dyslipidemia was higher in participants who perform less physical activity. TC and HDL-c dyslipidemia were significantly higher in participants with a history of DM than non-DM  and  ) of the study participants had at least one lipid profile abnormality that is compatible with a diagnosis of dyslipidemia according to NCEP-ATP III guidelines. The prevalence of TC ≥ 200 mg/dl, TGs ≥ 150 mg/dl LDL-c ≥ 130 mg/dl and HDL-c < 40 mg were 39.8%, 44.6%, 29.4%, and 53.5%, respectively. TC dyslipidemia was higher in males than females, but the difference was not statistically significant , followed by hypertensive heart disease 44 (16.36%)  and (95%CI) was 1.9(1.2–3.2) for TC ≥ 200 mg/dl and 2.3(1.4–3.87) for TGs ≥ 150 mg/dl. Past history of smoking, the cOR and (95%CI) was 2.2(1.1–4.3) for HDL-c < 40 mg/dl; while sedentary lifestyle, the cOR and (95%CI) was 5.7(1.9–16.7) for TC ≥ 200 mg/dl, 3.1(1.2–7.8) for TGs ≥ 150 mg/dl and 2.7(1.09–6.8) for HDL-c < 40 mg/dl. In addition, a history of DM was significantly associated with TG and HDL-c dyslipidemia, while a family history of hypertension disease was significantly associated with TC and LDL-c dyslipidemia.2 were significantly associated with TC dyslipidemia, the aOR) and (95% CI) were 4.5(1.4–14.6) and 6.7(1.4–32.5), respectively  and (95% CI) was 2.6 (1.4–4.8) for TC dyslipidemia and 2.4 (1.2–4.7) for TGs dyslipidemia. Hyperuricemia was significantly associated with LDL-c and HDL-c dyslipidemia, the aOR) and (95% CI) were 2.4(1.2–4.7) and 1.81.0–3.2), respectively. In addition, sedentary lifestyle and BMI ≥ 30 kg/m.2, respeTC, TG and LDL-c were positively correlated with WC and BMI, while TGs and LDL-c were positively correlated with age. In addition, TC and TGs were positively correlated with uric acid. However, TGs was negatively and significantly associated with cardiac disease duration Table .Table 4CDyslipidemia is the most important independent predictor of cardiovascular disease, leading to high morbidity and mortality in cardiac patients. Therefore, this cross-sectional study was conducted in a resource-constrained East African setting to determine the burden of dyslipidemia and its risk factors in cardiac patients.In this study, the overall prevalence of dyslipidemia was 76.6%  using the NCEP ATP III criteria and the rate was almost comparable with the study reported from Iran, which indicated that 78.9% of cardiac patients suffered from dyslipidemia . HoweverIn this study, dyslipidemia was higher in males (57.3%) than in females (42.7%). Conversely, the study reported from Iran , indicatIn this study, the most frequently observed dyslipidemia was low HDL-c (< 40 mg/dl), with a rate of 53.5%. This is almost comparable to the study conducted in Qatar, which was 56.8% . HoweverIn this study, the prevalence of TGs dyslipidemia was 44.6%. It was inconsistent with the rate reported from different studies: like 63% among CHD patients in India , 63.3% iIn addition, the prevalence of high TC in our study was 39.8%, which was higher than the study conducted in India, 23.3%  and CameThe prevalence of high LDL-c was 29.4% which was higher than the studies reported in Malaysia, 9% , and CamIn addition, in this study, the prevalence of TC dyslipidemia was 39.8% and this is not in line with the studies conducted in India , MalaysiRegarding risk factors, the present study showed that TC and TG dyslipidemia is significantly and positively associated with age > 54 years. This could be due to an age-related increase in postprandial dyslipidemia, insulin resistance, and age-related decline in ApoB/E receptor and sex hormones (estrogen and androgen) . In thisp > 0.05), which was comparable with the study reported from Sudan [The present study showed that sex, ethnicity, residence, alcohol consumption and hypertension have no significant effect on lipid profile (om Sudan . HoweverIn this study, obesity was associated with a higher risk of having hypercholesterolemia and the finding was in line with the study conducted in the Iranian adult population . This isWe found that DM is significantly associated with dyslipidemia among cardiac patients and this is a common phenomenon in patients with type 2 diabetes because insulin resistance or insulin deficiency impairs important enzymes and pathways in lipid metabolism .Furthermore, studies revealed that the association of hyperuricemia with dyslipidemia , 42. SimFirstly, we conducted a cross-sectional study, which cannot provide adequate evidence of causation regarding dyslipidemia and its risk factors. Secondly, we have not compared the findings with the control group because this study was conducted in the hospital, most people visit the hospital for medical purposes and it is difficult to get a sufficient number of apparently healthy subjects as a control group. Regardless of the depicted limitations, this study provides helpful information in the scarce data situation of Ethiopia.The results of this study showed that there was a high prevalence of dyslipidemia in cardiac patients based on the NCEP-ATP-III criteria. The most commonly observed dyslipidemia was low HDL-c, followed by TG, TC, and LDL-c dyslipidemia. In addition, older age, presence of diabetes, smoking habits, vegetable/fruit consumption status, body weight, abdominal obesity, and a FHHD, sedentary lifestyle, duration of treatment, and hyperuricemia are significantly associated with dyslipidemia. Therefore, regular assessment of lipid profiles is crucial to minimize further complications from dyslipidemia among patients with cardiac disease. In addition, intensive counseling of the patients with regard to physical activity, behavior change and diet modification is also mandatory. Furthermore, well controlled and large scale longitudinal studies are recommended to address other unexplained factors of dyslipidemia and hidden burden of dyslipidemia among cardiac patients at regional or national level.