Since there are no products in the European market labelled as low-FODMAP , patients with irritable bowel syndrome and non-celiac wheat sensitivity often consume gluten-free products. These naturally contain little FODMAP, but have poorer sensory properties and lower nutritional value. This study aimed to develop sensory attractive crackers with high-fibre and low-FODMAP content. Various gluten-free flours , pumpkin seed meal, chia seeds, flax seeds, rice protein, sweet potato, sourdough, and spices were used to develop nine formulations. Using a nine-point hedonic scale and ranking test, four best-scored products were selected for which descriptive sensory analysis was performed and nutritional value and fructan content were determined. Crackers made from maize and millet flour mixtures (ratio 1:2.5) with sourdough and with chia or flax seed addition were rated highest for overall impression . Generally, high-fibre content, hardness, chewiness, dark colour, and bitterness lower the acceptability of crackers, but the addition of spices and sourdough can improve their acceptability and marketability. The crackers could be labelled as “gluten-free”, “low-FODMAP” (<0.12 g/100 g), “naturally high-fibre” (7–10 g/100 g of which 17–23% are soluble), and “high in protein” (24–26 g/100 g). Non-celiac wheat sensitivity (NCWS) and irritable bowel syndrome (IBS) are the growing metabolic disorders for which an adapted and individualised diet is usually recommended as an integral part of the treatment. Low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diets show the best effect in alleviating the symptoms of IBS and NCWS. FODMAPs are important natural prebiotics and their intake affects the structure and function of the gut microbiota. However, they are also characterised by poor absorption in the small intestine, fermentability, and high osmotic activity, which can cause digestive problems in sensitive individuals. In fact, reducing FODMAPs is cited as more likely to improve symptoms in NCWS than eliminating gluten-containing products .An important principle of the low-FODMAP diet is the replacement of intolerable high-FODMAP foods with nutritionally equivalent low-FODMAP foods. This is a major challenge as avoiding FODMAP can easily lead to low intake of dietary fibre and micronutrients, which, if not compensated by suitable alternative sources of fibre, can lead to undesirable changes in the gut microbiota . TherefoThus, there are several strategies to produce low-FODMAP products. They can be produced either by selecting low-FODMAP ingredients in the product formulations or by using biotechnological tools to degrade FODMAP during the production process  ,10. WholIn the development of a new product, consumer acceptance continues to be the most important factor, while sensory analysis is the gold standard in assessing product acceptance. Consumers are attracted to good sensory attributes, and therefore, sensory methods are an important and integral tool that should be used in the new product development process . Sensoryhttps://www.fodmapeveryday.com/ accessed on 14 August 2022). The criteria that must be met for certification are not publicly available, and each product is evaluated individually. However, in general, products or formulations must not contain added FODMAPs, including fructo-oligosaccharides, inulin, and polyols (except sorbitol and mannitol), maltitol, xylitol, erythritol, lactitol, and isomalt. Among the certified products, there are only two cracker products labelled as “Low-FODMAP”.Currently, very few FODMAP-labelled products are available on the European market, due to the lack of definitions and EU legislation for FODMAPs. Low-FODMAP foods can be found among gluten-free products, but these are rarely sensory attractive and have low nutritional value . A good The aim of this study was to investigate the possibility of using different gluten-free wholemeal cereals, oilseeds, plant protein, sweet potato, sourdough, and spices in the development of nutritionally enhanced and sensory attractive crackers for consumers with IBS and NCWS. The first phase was the development of nine cracker formulations with high fibre but low fructan content; and the second phase involved selecting the four best rated crackers and evaluating them for their sensory description, nutritional value, and fructan content. The chemical composition of the developed crackers was compared with the chemical composition of two similar products available on the market.TM LV1 starter , spices , dry yeast , salt, and tap water. Raw materials were used without milling except chia and flax seeds which were ground in a coffee grinder until a particle size of <500 µm was achieved, and sieved using a laboratory rotary vibration sieve. Median particle size was determined by laser diffraction on a Mastersizer 2000 device  in combination with a dry dispersion unit (Scirocco 2000) at a pressure of p = 1 bar and a cell supply rate of 60%, in three replicates. The proximate composition taken from producers’ labels of main ingredients is shown in https://www.fodmapeveryday.com/product-category/collections/low-fodmap-certified-brands/ (accessed on 14 August 2022)). The ingredients in the one of the commercial crackers were black sesame, potato starch, brown rice, soy sauce, water, dextrin and salt, while the ingredients in the other commercial cracker were sesame, brown rice, rice flour and sweet potato starch and soy sauce.The cracker formulations contained combinations of different gluten-free raw materials, as these usually contain small amounts of FODMAP. The raw materials were white maize flour, wholemeal buckwheat, and millet flour  (median particle size D(50) ~300 µm), sweet potato puree , flax seeds , chia seeds , pumpkin seed meal (D(50) ~500 µm, PoljoPosavec Ltd., Dunjkovec, Croatia), and rice protein . The formulations also contained fat spread consisting of 59% vegetable oil , olive oil , LIVENDOThe chemical composition of the four best-rated crackers was determined by standard AACC methods  in two rDetermination of fructan and GOS content in white maize flour, millet, buckwheat, rice protein, chia seeds, flax seeds, pumpkin seed meal, and four selected crackers was performed according to the AOAC method 999.03, as previously described by Habuš et al. [In the first phase, nine formulations of crackers  were devEight of the nine types of crackers included the sourdough fermentation. To make sourdough, 20 g of flour mix (depending on the recipe), 35 mL of room temperature tap water, and 0.5% (flour basis) of LV1 starter were used. After fermentation in a lidded jar at 30 °C for 16 h, sourdough was added to the main dough mixture considering the amount of flour and water contained in the sourdough. The cracker F2 was made without sourdough using the “all-in” method. The cracker dough was prepared using a kitchen robot  according to the modified AACC 10-50D method . The metThe sensory analysis of the crackers was carried out at the Faculty of Food Technology and Biotechnology at the University of Zagreb, Zagreb, Croatia. A panel of nine experienced assessors (aged 23 to 52 years) who specialised in cereal products was selected. The training programme for the sensory panel included the identification and description of attributes and the procedures using the response scale . All of p < 0.05 set as the limit of statistical significance.Microsoft Office Excel 2016 and Statistica v.10  were used for the statistical data processing. The results are expressed as the mean value with standard deviation. Statistica was used to detect statistically significant differences between samples for which analysis of variance (ANOVA) was performed with the Tukey post hoc test, with a value of Since there is a limited number of studies dealing with FODMAP content in wholemeal cereal and oilseed flours, we determined the content of fructan in the flours used . White mTotal dietary fibre content in the raw materials used ranged from 2 to 38 g per 100 g of raw material . Chia seAccording to Coskuner and Karababa , flax seThe highest mineral content was found in pumpkin seed meal, followed by chia and flax seeds. Comparing the mineral contents of the flours, buckwheat flour is dominant in terms of minerals. Although the addition of buckwheat flour has a negative impact on the sensory acceptance of the product due to its characteristic taste, it contributes to the nutritional value of the product . The lowA hedonic sensory analysis and ranking test were used to determine the general acceptability and preference of crackers produced according to nine different formulations . Only fop = 0.930).The preference rank order is also presented in The results of the descriptive and hedonic sensory analyses of four best-rated crackers  are showp = 0.045) between the colour intensity of crackers F5 and F8 with an average value ≥8 as compared with the lighter F3 and F4, which had an average value of 5.9 for colour  was used which resulted in the lowest scores for odour intensity (average 4.8). Chives were used in cracker F4, pepper and wild garlic were used in cracker F5, and turmeric and dill were used in cracker F8; crackers F4, F5, and F8 were rated similarly for odour intensity (6.8–7.5) which was higher than cracker F3.p > 0.05) difference was found between the crackers in terms of intensity of overall taste and flavour, chewiness, granularity, solubility, dryness, and teeth adhesiveness.A bitter taste was not detected in the crackers during consumption, in contrast to a well detected bitter aftertaste (in the range 1.7–4.7) in all of the four crackers. No significant (p < 0.05) (mean scores 6.1 and 6.3), but not significantly harder than cracker F8 (mean score 7.4) (p > 0.05). The fat content in cracker F5 was lower than the fat content in the other three types of crackers, which most likely caused their higher hardness (Cracker F5 was rated as the hardest (mean score 8.6), significantly harder than crackers F3 and F4 (hardness . In addip > 0.05). The differences in the best-rated cracker F4 as compared with cracker F3 were the addition of flax seeds in the recipe and the use of chives, while in the cracker F3, chia seeds and Mediterranean seasoning mix was used.The results of the hedonic sensory analysis of the individual properties of the four best-rated crackers are shown in Previous studies on the addition of flax seeds in biscuit production have shown that partial replacement of wheat flour with ground flax seeds (up to 12%) does not affect the physical and sensory properties of the product . HoweverIf we compare the results of the hedonic and descriptive sensory analyses, crackers F3 and F4 differed significantly only in intensity of overall odour, which was higher for cracker F4, suggesting that the better acceptance of cracker F4 was influenced by the spices used.If we compare the results of the hedonic sensory analysis conducted on nine crackers with the sensory analysis conducted on four crackers in terms of overall impression, the best-rated crackers in both analyses were cracker F4, followed by cracker F3. However, in the second sensory analysis, crackers F5 were rated better than F8, while in first analysis it was vice versa.p < 0.05). Appearance, taste, and flavour, as well as texture in the mouth were rated better for cracker F5 than for cracker F8. Odour is the only sensory property that was rated better for cracker F8 than for cracker F5.Crackers F5 and F8 differed significantly from the better-rated crackers F3 and F4  were combined in cracker F5, while only buckwheat flour was used in cracker F8. In the research of Šimurina et al. , a wholep < 0.001) of minerals was found in crackers F5 and F8 as compared with crackers F3 and F4. The addition of pumpkin seed meal and buckwheat flour , but not from cracker F3 (p = 0.183). In addition, all the crackers were low in saturated fat. In the F3, F4, and F5 formulations, 31–35% of the energy value originated from fats rich in unsaturated fatty acids.Crackers made according to the F8 formulation had the highest fat content, significantly differing from crackers F4 and F5 . To achieve the target values for carbohydrates and proteins, the amount of fat should be reduced and the amount of proteins increased in our formulations. All the types of crackers were “high in fibre”, since they contained more than 15 g of fibre per 1000 kcal . MoreoveConsidering the content of soluble fibre, crackers F4, F5, and F8 would be suitable for IBS patients, while all of the four crackers would be suitable for patients who suffer from NCWS and celiac disease. Hence, it can be observed that higher total dietary fibre content contrasts important descriptive sensory properties of crackers such as taste and flavour, while soluble fibre content contrasts undesirable descriptive texture attributes and bitter taste .https://www.fodmapeveryday.com/product-category/collections/low-fodmap-certified-brands/fodmap-friendly-low-fodmap-certified/?paged=8 (accessed on 14 August 2022)). The crackers contain about 21 g of fats, 55–60 g of carbohydrates, 4–7 g of fibre, 10–14 g of proteins, and approximately 450 kcal per 100 g of product. If we compare our crackers with those from the market, it is evident that they have less fat, much more proteins and fibre, and still have low-FODMAP content. The reason for this is that our crackers had more complex compositions and more nutritionally valuable ingredients such as wholemeal flours and oilseed flours. Furthermore, our crackers were prepared with sourdough which contributed to their flavour and taste, but also assured low-FODMAPs [To the best of our knowledge, there are only two certified low-FODMAP crackers on the market, and they can be found in Australia  contribute to a higher nutritional value of crackers in terms of a higher content of protein, unsaturated fatty acids, and minerals. Moreover, crackers from wholemeal flours with a milder taste (maize and millet) are better accepted than those from buckwheat flour, which is characterised by a specific taste. At the same time, sweet potato and spices have a significant influence on the acceptance of the product, as does the addition of sourdough, which has the potential to improve the taste and appearance of the crackers. Unlike total dietary fibre content that obstructs important descriptive sensory properties of crackers such as taste and flavour, soluble fibre content confines undesirable descriptive texture attributes and bitter taste. Nevertheless, soluble fibre and fat content contrast crackers’ hedonic qualities. In the development of products with a high fibre content for IBS sufferers, special attention should be given to the proportion of soluble fibre in total fibre, not only for consumer acceptance, but also for health reasons. Future studies should investigate novel processing techniques in the production of snacks for IBS and NCWS patients, as well as their shelf life.


Undaria pinnatifida, has presented beneficial effects, which may be correlated with this species containing major bioactive compounds, such as carotenoids, fatty acids, and phytosterols. Marine carotenoid fucoxanthin is abundantly present in edible Undaria pinnatifida and features strong bioactive activities. The stem of Undaria pinnatifida is very hard to gnaw off and cannot be swallowed; therefore, it is usually discarded as waste, making it an environmental issue. Hence, making full use of the waste stem of Undaria pinnatifida is an urgent motivation. The present study aims to explore the optimal preparation technology of fucoxanthin from Undaria pinnatifida stems using supercritical carbon dioxide methods and provides approaches for the extraction and preparation of bioactive compounds from a waste seaweed part. With the comprehensive optimization conditions applied in this study, the experimental yield of fucoxanthin agreed closely with the predicted value by > 99.3%. The potential of α-amylase and glucoamylase to inhibit bioactive compounds was evaluated. The results demonstrated that the inhibition activity  of α-amylase (0.1857 ± 0.0198 μg/ml) and glucoamylase (0.1577 ± 0.0186 μg/ml) varied with extraction conditions due to the different contents of bioactive components in the extract, especially fucoxanthin (22.09 ± 0.69 mg/g extract). Therefore, this study confirmed supercritical fluid extraction technology to be a useful sample preparation method, which can effectively be used to prepare fucoxanthin from waste marine resources. This method can potentially be applied in functional food and related industries.In the recent years, edible brown seaweed,  As compared to conventional organic liquid extract, the SC-CO2 extract contains fewer polar impurities; therefore, subsequent purification or separation steps are rendered easier . In addition, the extraction efficiency of fucoxanthin can be significantly improved by adding ethanol as the entrainer , originally proposed by Box and Wilson , is char2 method was investigated for the effective extraction of bioactive compounds from un-utilized Undaria pinnatifida stems. RSM was designed by employing a BBD to systemically analyze the effects of extraction parameters, including extraction time, pressure, temperature, particle size, CO2 flow, and type of entrainer, on the yields of bioactive compounds, such as fucoxanthin, from the stem. This study will contribute to advancing the knowledge on ideal extraction conditions for obtaining maximal yields of bioactive compounds from the un-utilized stem of seaweed. Our findings can be used as a basis for further studies and provide scientific methods for the extraction and preparation of bioactive compounds from a waste seaweed part.In this study, the SC-COUndaria pinnatifida stem was collected from Kesennuma, Miyagi prefecture, Japan, and the harvest time is the middle of April.The brown seaweed Bacillus sp. and glucoamylase for Rhizopus sp. were purchased from Nacalal Tesque, Inc. . Fucoxanthin standard (≥ 98% purity), sodium dihydrogen phosphate dihydrate (≥ 99% purity), disodium hydrogen phosphate 12-water (99% purity), 1 mol/L sodium hydroxide solution, iodine (99.8% purity), and potassium iodide (99.5% purity) were purchased from Wako Pure Chemical Industries, Ltd. . Milli-Q water was used in these experiments. All reagents used in this study were analytical or high-performance liquid chromatography (HPLC) grade.High-purity carbon dioxide gas (99%) was supplied by Showa Denko Gas Products Co., Ltd. . The amylose B and α-amylase from Undaria pinnatifida stem sample was prepared according to the previous method  was used  with carbon dioxide  in the test sample was measured using previously described methods . AbsorbaHigh-performance liquid chromatography analyses were conducted using an HPLC system  equipped with a UV/VIS detector  and a hybrid silica-based ODS column . The HPLC conditions were similar to those used in earlier studies with minor modifications , 59, 60.2: 5 mM KI (1:1) dissolved in water]. Initially, the same amount (20 μl) of solutions 1, 2, and 3 was taken in 0.2-ml PCR tubes and incubated in a PCR thermal cycler  to activate the enzymatic reaction at 40°C. As the extract concentrations in solution 1 were 10–300 μg/ml, the final concentration of the extract during this enzymatic reaction process corresponded to 3.33–100 μg/ml, respectively. After 45 min of incubation, 1 M HCl (20 μl) was used to stop the enzymatic reaction. Subsequently, an iodine reagent (100 μl) was used for color development. A microplate reader  was then used at 580 nm to measure absorbance. Enzyme activity was measured as the difference in the absorbance of the enzyme-treated sample compared with that of the untreated sample. The inhibitory activity was expressed as a percentage of difference in absorption between treated and untreated samples. To examine the practicality of the extract as an enzymatic inhibitor, the inhibitory activity of acarbose was also evaluated as the positive control. Acarbose inhibits α- amylase and glucoamylase  were determined graphically (percent of inhibition versus log inhibitor concentration) by interpolation from the inhibitions determined on the stem extracts and bioactive compounds . All the assays were performed in triplicates and the data were expressed as mean ± standard deviation. Statistical analysis was performed using GraphPad Prism software , SigmaPlot software , or SPSS software for Windows (version 17.0). The 2 extraction technology used in this study will focus on how to obtain fucoxanthin efficiently. Although fucoxanthin is abundant in every part of Undaria pinnatifida, previous studies do not report details of its optimal extraction by SC-CO2. In addition, only a few researchers have obtained fucoxanthin from the waste part of Undaria pinnatifida. Therefore, the extraction conditions of fucoxanthin cannot be inferred from previous research methods. Therefore, new experiments must be designed independently for each variable to explore the best scientific method to obtain fucoxanthin from seaweed. Undaria pinnatifida and the extraction conditions for SC-CO2 used in the current research. Important information or conclusions can be derived from Researchers found that seaweed extracts contain a variety of beneficial active substances, such as polyphenols, flavonoids, carotenoids, and so on. As a unique active substance, fucoxanthin is abundant in brown algae. Therefore, the design of SC-CO2 optimization. According to the characteristics of RSM, we divided the six independent variables into two groups, that is, extraction temperature, time and pressure as one group, and sample particle size, CO2 flow rate, and entrainment dose as the other groups. To make the design more scientific reference, these two groups of design models are independent and do not affect each other. The purpose is to obtain the best extraction process through the above two experimental design groups. Therefore, RSM combined with the BBD was selected to investigate six independent variables involved in SC-CO2 extract, and TFC  is a quantitative index of active substance in the SC-CO2 extract. This was in agreement with our previous research, although the amount of fucoxanthin was lower than TFC, and the trend of its variability and response surface plot were similar to that of TFC , regardless of CO2 flow rate and entrainer amount. These amounts were higher as compared to the amounts of bioactive compounds on larger particles of 450 and 800 μm diameters. Therefore, the best yields of TFC (30.78 ± 0.07 mg/g) and fucoxanthin (21.86 ± 0.10 mg/g) were obtained under Experiment 21   .New experiments were designed to explore the effects of extraction temperature, pressure, and time on the yield of fucoxanthin in the next study and to verify the aforementioned conclusions.2 . According to Machmudah et al. , it could be seen that regardless of whether CO minimal .2 flow rate, and entrainer were set at 240 min, 50°C, 6000 psi, 100 μm, 4 ml/min, and 3.125 ml, respectively. To ensure that the predicted results did not deviate from the actual values, the following modified parameters were experimentally reviewed: extraction time of 230 min, temperature of 53°C, pressure of 5900 psi, and entrainer of 3.0 ml. The values obtained from actual experiments (p > 0.05), demonstrating the effectiveness of the RSM model. A good correlation between these results confirmed that the RSM was sufficient to reflect the expected optimization. The results showed that the experimental values were in good agreement with the predicted values. The model from BBD accurately and reliably predicted the bioactive compounds, especially fucoxanthin, from steam by SC-CO2 extraction.The applicability of the model equation to predict the optimal response value was tested using slightly modified optimal parameters. We compared the maximum predicted yield and experimental yield of bioactive compounds. Additional experiments using the predicted best parameters for the extraction of bioactive compounds were as follows: extraction time, pressure, temperature, particle size, COeriments  agreed wSaccharina japonica, Undaria pinnatifida, Sargassum fusiforme, and Eisenia bicyclis, etc. Research shows that each gram of macroalgae contains 0.1–1.0 mg fucoxanthin  new regulations on the use, residue production, and contamination control of toxic chemicals; (2) products from traditional processing technology cannot meet the market demand for higher quality products; and (3) consumers’ concerns about the safety of final products. Therefore, it is necessary to develop extraction technologies that can provide high-quality extracts. In this study, we have proven that supercritical fluid extraction is a clean and efficient extraction technology for bioactive compounds from seaweed. Although this technology has some shortcomings, such as the requirement of a huge investment in the early stage of setup, its advantages are obvious in the long term. With the rapid development of commercial applications of supercritical technology, more research studies are focusing on the real application of this technology, rather than remaining limited to laboratory research.Like fucoxanthin, which is the focus of this research, it has great commercial potential. At present, the price of high-purity fucoxanthin (more than 90%) raw materials in the market is as high as 60,000 US dollars a kilogram . In addi2 extraction of an important bioactive functional component, fucoxanthin, from unused Undaria pinnatifida stem. The results demonstrated that extraction temperature and pressure, particularly, particle size, are the key parameters controlling the extraction of fucoxanthin, whereas the impact of other factors is limited. In terms of bioactive compounds, high yields of fucoxanthin were found in Undaria pinnatifida stem. Hence, this study’s experimental results highlight several key advantages of SC-CO2: (1) use of less solvent/CO2 consumption; (2) less residual solvent in the extract, even in the case of co-solvent; (3) the rationality of the SC-CO2 process, such as no excessive separation or purification steps, high purity of the bioactive product (fucoxanthin); and (4) controllability of the temperature in the extraction process, allowing adaptation of the production to the thermally sensitive fucoxanthin. Therefore, SC-CO2 extraction of fucoxanthin from seaweed stem may be used to develop dietary supplemental products for the management of different biomolecules, such as the digestion of amylose in dietary starches, and to improve the potential for their effective utilization. Therefore, this study may become the basis for future research on a large-scale extraction system in food and pharmaceutical industries and can accelerate the sustainable utilization of commodity waste from seaweed.In the present study, a response surface methodology with the BBD coupled with a numerical optimization technique was applied to optimize and study the interactive effects of different process variables on the SC-COThe original contributions presented in this study are included in the article/SY: conceptualization, investigation, writing—review and editing the manuscript. LN, MS, YL, and TH: review the manuscript. All authors have read and agreed to the published version of the manuscript.


To express a global view of care quality in major causes of mortality and morbidity in children and adolescencesWe used primary epidemiologic indicators from the Global Burden of Disease 1990–2017 database. We have created four secondary indices from six primary indices in order to assess the care quality parameters. We conducted a principal component analysis on incidence, prevalence, mortality, Years of Life Lost (YLLs), Years Lived with Disability (YLDs), and Disability Adjusted Life Years (DALYs) to create an index presented by quality-of-care index (QCI) to compare different countries.The global QCI scores of respiratory infection, enteric infection, leukemia, foreign body aspiration, asthma, epilepsy, diabetes mellitus, dermatitis, road injury, and neonatal disorders have improved remarkably. These causes showed equal distribution of qualified care for both sexes. The global trend of QCI score for mental health showed a steady pattern during the same time and disparities favoring females was evident. The quality of care for these causes was notably higher in developed areas.The global QCI revealed a universal growth in major causes of death and morbidity in <20y during 28 years. Quality of care is an associate of the level of country’s development. Despite effective interventions, inequities still remain. Implementation of policies to invest in quality improvement and inequality elimination is needed. Health of children and adolescences is important not only as a human right issue, but as an important determinant of development and sustainability. Investments in children health contribute to social security and economic growth . This spPrevious studies on this issue were commonly descriptive , and allIn this study we aim to express a global view of quality care in major causes of mortality and morbidity in children and adolescences. In order to evince quality of care and early detection status and trends of different SDI quintiles in recent decades, we created a novel index by the name of quality-of-care index (QCI). Among the top leading causes of DALYS  and chalWe used the Global Burden of Disease (GBD) data from 1990 to 2017, which is available in GBD compare in Institute for Health Metrics and Evaluation (IHME) website in causes section as: A.2 (Respiratory infection and tuberculosis), A.3 (Enteric infection), A.6.2 , B.1.28 (Leukemia), B.3.3 (Asthma), B.5.3 (Idiopathic epilepsy), B.6 , B.8.1 (Diabetes mellitus), B.9.1 (Dermatitis), C.1.1 (Road injury), C.2.8 (Foreign body) .The data this study was secondary and no individual data is used. The confidentiality of the data is preserved.We created four secondary indices from six primary indices, in order to assess the quality of care parameters . These iIn order to summarize all of these indicators, Principal Component Analysis (PCA) was performed. The first component extracted from PCA was considered as the QCI, which is scaled into 0 to 100 range, with higher scores representing better quality of care. We calculated QCI and SDI quintiles on global scale. SDI is a measure of socio-demographic development in GBD studies, computed by a composite average of the rankings based on average income per person, educational attainment, and total fertility rate (TFR). Classifications of SDI are high, high-middle, middle, low-middle, and low quantiles. It is important to know calculated QCI for each scale, is a compile of 28-year data of that scale. In order to find outliers, 6 sigma approach is used. Mean and standard deviation of indicators are calculated and measures out of μ-3σ, μ+3σ considered as outliers.Age classification was in seven groups: early neonatal (0-7d), late neonatal (7-28d), post neonatal (1-12m), 1-4y, 5-9y, 10-14y, 15-19y. The QCI is calculated for each age group, sex, cause, and year in global scale, SDI quintiles, and 195 countries and trends have been depicted disparity of care in different ages.To calculate the gender disparity, we made gender disparity ratio (GDR), which is QCI score in females divided by QCI score in males.Then we calculated this ratio on global scale, SDI quintiles, and all countries. Ratios near one demonstrate the least disparity between two sexes. Values higher or lower than one shows inequality favoring one sex.Primary indicators are reported with a 95% uncertainty interval (UI). Estimation and trend of changes were significant when UIs during time do not overlap. All the statistical analyses, plots and numbers created in this study were performed by R v3.6.1 and RStudio v1.0.136 .We have evaluated the correlation between the QCI and Healthcare Access and Quality Index (HAQI)  by applyGlobal death rate in under 20y population was 255.91  per 100,000 in 2017, which decreased near 50% between 1990 and 2017 . Total DGlobal death rates and DALY decreased in <20y population between 1990–2017 . 23.9% oGlobal deaths and DALY regarding these causes decreased in <20y population between 1990–2017 . This caGlobal deaths and DALY due to diarrheal, typhoid and paratyphoid diseases notably decreased in <20y population between 1990–2017 . It takeDALYs due to mental disorders -including (ordered by the highest burden to the lowest) conduct disorder, anxiety disorders, depressive disorders, idiopathic developmental intellectual disability, autism spectrum disorders, bipolar disorders, eating disorders, attention-deficit/hyperactivity disorders (ADHD) and schizophrenia- in <20y population, increased between 1990–2017 . Mental Global death and DALY due to road injuries in <20y population decreased between 1990–2017 . 2% of DDALYs due to dermatitis in <20y population increased between 1990–2017 . 0.8% ofThe rate of DALY in population of >20y decreased between 1990–2017 . It takeDeaths and DALY due to asthma in <20y population reduced during a period of 28 years . Asthma Global deaths and DALY in <20y due to foreign body decreased between 1990–2017 . 0.6% ofGlobal deaths and DALY due to leukemia in <20y population decreased between 1990–2017 . LeukemiRate of DALY due to DM type1 (T1DM) and type2 (T2DM) in <20y population, decreased during 28 years . DM takeSignificant Improvement of the global QCI score in children and adolescents for respiratory infection, enteric infection, leukemia, foreign body aspiration, asthma, epilepsy, DM, dermatitis, road injury, and neonatal disorders during a period of 28 years is a marker of better pediatric health care. Mental health shows a very slow increasing pattern and disparities favoring females is evident. Evidences in 1990 shows a better condition of care pro girls in epileptic disorders for 1-4y  further detection of T1DM  and T2DMDALYs due to mental disorders in children and adolescents has raised over time, therewith unsatisfying trend of improvement in quality of care. Implementation of mental health policies for children and adolescents is still a challenge in low setting areas, which could be due to low health literacy, political unwillingness, lack of a global agenda for mental health for children, stigma and shortage of resources . Gender Dermatitis has different pattern which could be due to the following explanations. 1) Limited data, few countries reported national registry data 2) Dermatitis is more prevalent in developed countries  cases per 100,000 in low SDI versus 8648.52 cases in high SDIs). The higher prevalence of dermatitis in high SDI regions is related to the theory of microbiome, which indicates that a higher exposure to microbes could have a protective impact on atopic dermatitis . 3) In NThe diagnosis of foreign body aspiration at the right time and emergent medical interventions, along with preventive educations are comprehensive strategies to decline accidents leading to death . The uneIn this study we report the situation of care quality for important causes of mortality and morbidity in children and adolescents by sex and age, which is a novel report among the burden of disease studies. While IHME reported HAQI  only by 32 different causes, and they did not report sex or age differences .There are several measures estimated and extracted from different models in GBD studies. Disparities could be found in some measures due to the following reasons: 1) as a result of poor capacity of that model in estimating specific conditions like rare events, 2) it could represent a real disparity in health outcomes, for example an odd prevalence of a disease in a country due to a poor health coverage for that specific disease. At first, we chose 30 causes, but according to the challenges in availability and validity of data, we have limited the study to 11 causes. Unfortunately, data from many countries is missing in section GHDx in IHME website which disrupts global resolutions. Based on computational challenges, we have not calculated uncertainty for QCI score.Global quality of care index which was introduced in this study revealed a universal growth from 1990 to 2017 in major causes of death and morbidity in children and adolescents. Except for mental health which represented a gender disparity in condition of care pro females, other causes showed equal distribution of qualified care for both sexes. We demonstrated that care quality is an associate of the level of country’s development. Hence, despite the recent achievements in the management of major causes of mortality and morbidity in children and adolescents, farther investments are required to allocate the resources more effectively and to overcome inequities.S1 File(ZIP)Click here for additional data file.S2 File(PDF)Click here for additional data file.


Acute myeloid leukemia (AML) is a malignant clonal disease of the myeloid hematopoietic system. Clinically, standard treatment options include conventional chemotherapy as well as hematopoietic stem cell transplantation. Among them, chemotherapy has a remission rate of 60% to 80% and nearly 50% relapse in consolidation therapy. Some patients have a poor prognosis due to the presence of unfavorable factors such as advanced age, hematologic history, poor prognosis karyotype, severe infection, and organ insufficiency, which cannot tolerate or are not suitable for standard chemotherapy regimens, and scholars have tried to find new treatment strategies to improve this situation. In the pathogenesis and treatment of leukemia, epigenetics has received attention from experts and scholars.  To investigate the relationship between OLFML2A overexpression and AML patients.  From The Cancer Genome Atlas, researchers used the data of OLFML2A gene to analyze and study the pan-cancer using R language and then divided the high and low levels of this protein into two groups to study its relationship with the clinical characteristics of the disease. The relationship between the high levels of OLFML2A and various clinical features of the disease was studied with emphasis on the relationship between the high levels of OLFML2A and various clinical features of the disease. A multidimensional Cox regression analysis was also performed to study the factors affecting patient survival. The correlation between OLFML2A expression and immune infiltration through the immune microenvironment was analyzed. The researchers then conducted a series of studies to analyze the data collected in the study. The focus was on the relationship between the high levels of OLFML2A and immune infiltration. Gene ontology analysis was also performed to study the interactions between the different genes associated with this protein.  According to the pan-cancer analysis, OLFML2A was differentially expressed in different tumors. More importantly, the analysis of OLFML2A in the TCGA-AML database revealed that OLFML2A was highly expressed in AML. The researchers found that the high levels of OLFML2A were associated with different clinical features of the disease, and that the expression of the protein was different in different groups. Those patients with the high levels of OLFML2A were found to have substantially longer survival times compared to those with low-protein levels.  The OLFML2A gene is able to act as a molecular indicator involved in the diagnosis, prognosis, and immune process of AML. It improves the molecular biology prognostic system of AML, provides help for the selection of AML treatment options, and provides new ideas for future biologically targeted therapy of AML. Acute myeloid leukemia (AML) is a malignant disease of the hematological system with strong biological and clinical heterogeneity. Currently, patients are generally stratified according to their cytogenetic and molecular biological findings to predict their treatment outcome . In pracThe OLFML2A (olfactomedin-like 2A) gene is located on chromosome 9q33.3 and encodes a protein also known as “photomedin-1,” which belongs to the OLFM  family IV . OlfactoOLFML2A is a member of OLFM family IV, which contains at least eight exons spanning 37.7 kb and encodes a protein with an olfactomedin structural domain at the C-terminus and a unique serine/threonine region that distinguishes it from other proteins in the family, two to three potential glycosylation sites at the N-terminus, and homodimers or oligomers with disulfide bonds. Northern-blot of different tissue specimens from mice showed that OLFML2A transcription products were not found in the brain tissue . OLFML2ABased on this, from The Cancer Genome Atlas, researchers analyzed the data using OLFML2A gene data, analyzed and studied pan-cancer using R language, and then divided the high and low levels of the protein into two groups in order to study its relationship with the clinical features of the disease. Finally, it was concluded that the OLFML2A gene, as a molecular indicator, can be involved in the diagnosis, prognosis, and immune process of AML and has the potential to be a reliable prognostic assessment indicator W and a potential therapeutic boot point for AML patients.https://portal.gdc.cancer.gov/). We excluded the insufficient cases or missing data in the later information processing. The genomic expression information of OLFML2A was calculated from the TCGA database by high-throughput sequencing. Because all information was publicly available, no ethical approval was required.We collected TCGA-AML expression profiles and clinical information from TCGA Genomic Data Commons Data Portal (https://timer.cistrome.org/) 16 to observe differences in OLFML2A expression in tumors and nearby normal tumor tissue or particular tumor subtypes in the TCGA program.Pan-cancer analysis was performed through the TIMER2  network  between OLFML2A mutations. In addition, OLFML2A was split into high and low expression groups. The OLFML2A expression was judged in relation to overall survival by confirming the high and low OLFML2A expression based on the median. We applied survROC software to measure the accuracy of risk scores on prognosis using time-dependent subject operating characteristic (ROC) curves. We conducted univariate and multivariate analyses of risk scores after adjusting for age, sex, race, BM blasts, PB blasts, Cytogenetic risk, and FAB classifications. In addition, we analyzed the expression of OLFML2A with different clinicopathological features, and we investigated the association of OLFML2A expression with BM cells, cytogenetic risk, FAB classification, IDH1 R132 mutation, IDH1 R132 mutation, NPM1 mutation, and race.c-index to estimate nomogram accuracy.Since the development of nomograms, they have been used to forecast cancer prognosis. This method uses a statistical method to score various factors, such as age, gender, and the TNM stage. It can then produce a total score that provides a personalized estimate of the likelihood of the disease returning. In the study, the researchers used nomograms to predict the likelihood of patients with cancer returning. The R package rms generated them. The nomograms were then validated by implementing a series of calibration curves. Subsequently, we utilized the The researchers then performed a series of studies to analyze the data collected from the studies. They first used a computer program known as the CIBERSORT deconvolution to determine the relative composition of immune cells in each sample. Then, they performed an immune differential analysis to study the two groups' immune cell content differences.The cluster profile package was used for GO and KEGG enrichment analysis and underlying biological pathways that were likely to adjust the cancer development. They were also able to identify promising signals that could be linked to the disease.P < 0.001).To detect the differential expression of OLFML2A, we first investigated OLFML2A gene expression in 33 human cancers in TCGA using the TIMER database. Compared with normal samples, OLFML2A had higher expression in 27 cancers, including LUSC, BLCA, DLBC, BRCA, CESC, GBM, COAD, ESCA, KIPR, HNSC, KIRC, LGG, LAML, LUAD, READ, LIHC, PAAD, OV, PRAD, STAD, CHOL, PCPG, SKCM, TGCT, THYM, UCEC, and UCS, shown in Figure 1(a). By comparing the expression of OLFML2A gene in AML and normal samples, OLFML2A had a large overexpression in AML ; P < 0.05; We grouped high and low OLFML2A gene expression, and the correlation between OLFML2A gene expression and clinical features were explored. We incorporated age, grade, BM blasts, cytogenetic risk, FLT3 mutation, IDH R132 mutation, IDH R140 mutation, NPM1 mutation, PB blasts, RAS mutation, and WBC count for picture mapping. After analyzing the data collected from the studies, the researchers concluded that the high levels of the OLFML2A were different from the low levels of the protein. They also noted that the difference was significant when it came to age, BM blasts, and FLT3 mutations (P < 0.001) ). Figure 3(a) shows 0.977, indicating the area under the curve (AUC) value.Compared with high-risk patients, according to Kaplan–Meier survival curves, the survival of low OLFML2A expression patients was longer  is a common aggressive hematologic malignancy characterized by impaired leukocyte maturation and excessive proliferation of hematopoietic stem cells, which can spread to other organs such as the central nervous system, skin, and gums. Due to impaired normal hematopoietic function, AML patients often present with anemia, bleeding, and severe infections . In the β-catenin signaling pathway, which leads to upregulation of amyloid precursor protein (APP) expression and a decrease in the degree of stable β-catenin, resulting in having reduced MYC, CD44, and CSKN2A2 expression, thereby inhibiting cell proliferation and promoting apoptosis [OLFML2A is an abnormal protein that can be found in various tissues such as the breast, colon, ovary, and liver . Researcpoptosis , 22.Furthermore, by exploring the significance of OLFML2A expression in many clinical parameters, we found an association between OLFML2A and AML survival and clinical features. This study performed an immune cell infiltration analysis to gain insight into the role of OLFML2A. From The Cancer Genome Atlas, researchers used OLFML2A gene data to analyze the data. Pan-cancer was analyzed and studied using the R language. They then divided the high and low levels of the protein into two groups to study their relationship with clinical features of the disease. The researchers then conducted a series of studies to analyze the data collected from the study. They focused on the relationship between the high levels of OLFML2A and various clinical features of the disease. They also performed a multidimensional Cox regression analysis to examine the factors that affect patient survival. We analyzed the correlation between OLFML2A expression and immune infiltration in the immune microenvironment. The researchers then conducted a series of studies to analyze the data collected from the study. They focused on the relationship between the high levels of OLFML2A and immune infiltration. They also performed gene ontology analysis to examine the interaction between different genes associated with the protein. OLFML2A was differentially expressed in a variety of tumors based on pan-cancer analysis, including the brain cell counting system, DLBC, ESCA, BRCA, CHOL, LGG, COAD, lipocytes, Kipres, GBM, chronic cell count, oligosaccharide nucleic acid, oligos nucleic acid, adipocyte leukocyte leukemia, adipocyte count enzyme, hyaluronidase, cycloplasmic carcinoma, growth hormone, paclitaxel leukocyte leukemia, prostaglandin, cerebroside leukocyte acid, goitre, and auscocis. In addition, the analysis of OLFML2A in the TCGA-AML database revealed that OLFML2A is highly expressed in AML. The researchers found that high OLFML2A levels were associated with different clinical features of the disease. They also noted that protein expression was different in different groups. Patients with the high levels of OLFML2A were found to survive longer compared to those with low-protein levels. The researchers found that the high levels of OLFML2A were associated with various clinical features of the disease. They also noted that the protein was expressed differently in different groups. Some of these clinical features include BM primitive cells, cytogenetic risk, and IDH1 R132 mutations. Using columnar line graphs, it was possible to predict patient survival based on OLFML2A levels. A relationship was also found between this protein and the growth of acute lymphoblastic leukemia. In the immune microenvironment, the researchers discussed the positive correlation between OLFML2A and various immune cell activities. In parallel, we completed a GO analysis. The CC terminology encompasses “encapsulated vesicle membrane,” “cell-matrix junction,” “focal adhesion,” “focal adhesion,” and “cell-matrix junction.” BP terms include “autophagy regulation,” “positive regulation of phosphatase activity,” “sterol metabolic process,” and “phosphorylation.”The OLFML2A gene is able to act as a molecular indicator involved in the diagnosis, prognosis, and immune process of AML. It improves the molecular biology prognostic system of AML, provides help for the selection of AML treatment options, and provides new ideas for future biologically targeted therapy of AML.


Previous studies have paid attention to media as an important channel for understanding organ donation knowledge and have not divided groups according to the degree of media use to study their differences in organ donation. Therefore, the purpose of this study is to explore the influence of media use on organ donation willingness and the influencing factors of organ donation willingness of people with different media use levels.A cross-sectional study of residents from 120 cities in China was conducted by questionnaire survey. Using Mplus 8.3 software, the latent profile analysis of seven media usage related items was made, and multiple linear regression was performed to analyze the influence of varying levels of media use on organ donation willingness of different population.P < 0.001) were positively correlated with their willingness to accept organ donation, residents who used media occlusion  were negatively correlated with their willingness to accept organ donation. The influencing factors of residents' accept willingness to organ donation were different among the types of occluded media use, ordinary media use and high-frequency media use.All the interviewees were divided into three groups, namely, “Occluded media use” (9.7%), “Ordinary media use” (67.1%) and “High-frequency media use” (23.2%). Compared with ordinary media use, high-frequency media population (β = 0.06, It is necessary to formulate personalized and targeted dissemination strategies of organ donation health information for different media users. Organ transplantation is an effective method for the treatment of end-stage organ failure, which is widely practiced around the world . The orgAlthough previous studies have paid attention to the relationship between media and organ donation, they have not divided groups according to the degree of media use to study the differences in organ donation. Studies have shown that when the audience gets information, they will form three groups of people. First, news avoiders who do not contact the mass media . Second,The study protocol was approved by the Institutional Review Committee of Jinan University (JNUKY-2021-018), Guangdong, China. All respondents have informed consent and voluntarily participated in the survey.Inclusion criteria for this study: (1) The nationality of the People's Republic of China; (2) Age ≥12 years; (3) China's permanent resident population ; (4) Participate in the study voluntarily and fill in the informed consent form; (5) Participators can complete the network questionnaire survey by themselves or with the help of investigators; (6) Participate can understand the meaning of each item in the questionnaire.Exclusion criteria include: (1) inconvenient movement, confusion, mental disorders; (2) Those who are participating in other similar research projects; (3) People are unwilling to cooperate.Multi-stage sampling was used. First, the provincial capitals and four municipalities of 23 provinces and five autonomous regions in China were directly included, and 2–6 cities, a total of 120 cities, were selected from the non-provincial-level administrative regions of each province and autonomous region by random number table method. At least one investigator or one investigation team ( ≤ 10 people) were openly recruited in these cities. Based on the results of the seventh national census, the residents of these 120 cities were sampled with quotas , which basically accords with the population characteristics of China. With the help of Questionnaires Platform, the investigators distributed questionnaires to the public one-on-one, and the respondents answered by clicking the link, and the investigators entered the questionnaire number. If the respondent has thinking ability but not enough action ability to answer the questionnaire, the investigator will query and fill in the questionnaire instead of him. The survey was conducted from July 10, 2021 to September 15, 2021.The questionnaire included social demographic information , media use, social support, depression, anxiety, pressure and willingness to accept organ donation. Among them, media use, pressure and willingness to accept organ donation were self-designed scales, while social support, depression and anxiety were international general scales.The research team designed the questionnaire after consulting books and literature scientifically and comprehensively. Before the questionnaire was officially used, experts consulted and discussed on June 7, June 11, June 15, June 18, July 3, and July 8, 2021. The consulted experts were all senior professional titles and regional representatives. Specialties include social medicine, health education, health statistics, health management, psychology, humanities, journalism and communication, pharmacy, nursing, sociology, philosophy, etc.Residents' willingness to accept organ donation was reported by the residents themselves . Use a sThe self-made media usage scale was used to measure the type and degree of media usage. Through scientific and comprehensive access to books and literature, the research team designed the questionnaire , 28, andThe PSSS was used to measure social support . PSSS waThe depression was measured by 9-Item Patient Health Questionnaire . The subThe anxiety was measured by 7-item generalized anxiety disorder (GAD-7). The subjects made self-evaluation based on their own situation in the past two weeks, and evaluated anxiety disorder according to the results of self-evaluation scores. GAD-7 had good reliability, as well as criterion, construct, factorial, and procedural validity . There aThe self-made pressure scale was used to measure the pressure . Self-evx2) test was used for comparison between groups, and classified variables were expressed by frequency. The potential profile of seven items used by media was analyzed by Mplus8.3 software, the smaller the values of Akaike Information Criteria (AIC) and Bayesian Information Criteria (BIC) were, the better the LPA fitting model was. The entropy value was between 0 and 1, and the closer to 1, the more accurate the classification. The significant difference between Lomendell-rubin (LMR) and Bootstrap Likelihood Ratio Test  indicates that K-type model was superior to K-1 model. Gradually increase the number of categories in the model from the initial model until the model with the best fitting data was found. On the basis of retaining the best category model, SPSS26.0 software was used for stepwise regression analysis. P < 0.05 (two-side) is statistically significant.Continuous variables were expressed by M±SD, Chi-square (P < 0.001) showed that the models of Class 2, Class 3, Class 4 and Class 5 fit well, and the value of Entropy was closest to 1 when it was in Class 4, followed by Class 3. Combined with the model diagrams of various categories, the classification models of three potential categories  were finally selected as the classification of residents' media usage frequency. The average probability of residents belonging to each category was between 95 and 98%, indicating that the results of the three models are reliable, as shown in Selected 1–6 potential profile models to analyze the frequency of media usage. The results showed that the values of AIC, BIC, and aBIC decreased with the increase of the number of classifications. The two indexes of LMR and BLRT  was higher than that in category C1 but lower than that in category C3. Therefore, this category was named “Ordinary media use”. Category C1 subjects accounted for about 9.7% of the total subjects, and the scores of each item (12.515 ± 1.788) were not high, and were significantly lower than those of C2 and C3. According to its scoring characteristics, this category was named “Occluded media use”. Category C3 subjects accounted for about 23.2% of all subjects, and its score (24.571 ± 3.510) was significantly higher than that of C1 and C2. Therefore, this category was named as “High-frequency media use” see .A total of 11,031 questionnaires were collected. Among the participants, 5,998 (54.4%) were females, 4,665 (42.3%) were younger than 30 years old, 6,360 (57.7%) were non-agricultural registered permanent residence, 8,008 (72.6%) were urban residents, and 6,487 (58.8%) had college degree or above see .Based on the analysis of the potential profile of media use, it was found that the number of residents aged less than 30 (55.4%) was the largest among the ordinary and high-frequency media users. Among the media- occluded people, the majority (42.5%) had primary school education or below. In the cases of no depression (49.5%), no anxiety (61.3%), and mild stress (26.2%), people with ordinary contact with media accounted for more, while in the cases of severe depression (6.1%), severe anxiety (6.4%), and severe stress (11.5%), people with high frequency of media use accounted for more.P < 0.05) in terms of age, permanent residence, registered permanent residence, education level, marital status, number of houses, number of children, number of brothers and sisters, debt, religious belief, anxiety, depression and stress, etc., which indicated that these factors had significant influence on residents' willingness to accept organ donation.The differences of residents' willingness to accept organ donation were statistically significant , people with “High-frequency media use” followed (582), and people with “occluded media use” were the least (150). However, in their respective categories, “High-frequency media users” accounted for 22.83%, followed by “Ordinary media users” accounted for 20.92%, and “occluded media users” accounted for 14.06% of the lowest.P < 0.001) were positively correlated with their willingness to accept organ donation, residents who used media occlusion  were negatively correlated with their willingness to accept organ donation.As shown in P < 0.001) and non-agricultural registered permanent residence  were more willing to accept organ donation. Male , older , residents with religious beliefs  were less willing to accept organ donation. Among individual social support, friend support  and other support  could enhance residents' willingness to accept organ donation. On the contrary, family support  could hinder residents' willingness to accept organ donation.Residents with college level or above , moderate anxiety , moderate stress , severe stress  and high support from friends  were more willing to accept organ donation. Other support  hindered residents' willingness to accept organ donation , non-agricultural registered permanent residence , mild anxiety , moderate anxiety  and severe stress  were more willing to accept organ donation. Male , had religious beliefs  and residents with children  were less willing to accept organ donation. In social support, friends' support  and other support  increased residents' willingness to accept organ donation, family support  hindered residents' willingness to accept donations , moderate pressure  and severe pressure  were more willing to accept organ donation. Older residents  with high frequency of media exposure are less willing to accept organ donation , Guangdong, China. The participants provided their written informed consent to participate in this study.FG and YJ provided the formal analysis, writing—original draft, and writing—editing. YW and XS provided the conceptualization and methodology. FG and YW provided the validation. JZ, MC, XJ, and YW provided the writing—review. All authors contributed to the article and approved the submitted version.The scientific research project of Shaanxi Provincial Education Department in 2021-the key research base project of philosophy and social sciences (Grant No. 21JZ017). It is the achievement of the National Cultural Research Center along the Southwest Silk Road of the State Ethnic Affairs Commission.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


SD were computed and presented by using tables and figures. A bivariable and multivariable binary logistic regression analysis was conducted to assess the association between factors and outcome variables.Motivating proper nutrition during childhood is the basis for optimal health, learning, productivity, and social wellbeing throughout life. Stunting is among the major public health problems. According to the Ethiopian mini demographic and health survey, the prevalence of stunting among under five children was 37%. In addition, stunting has a trans-generational effect on a mother’s nutritional status. However, evidence on the causal contribution of maternal employment to stunting among under five children is not well understood in Ethiopia. This study aimed to compare the stunting status and associated factors among under five children of employed and unemployed mothers in the Gurage Zone, Southern Ethiopia, in 2021. A community-based comparative cross-sectional study was conducted among 671 (330 employed and 341 unemployed) randomly selected mother–child pairs in the Gurage Zone, Southern Ethiopia. A pretested semi-structured tool and validated anthropometric measurements were used to collect the data. The data were entered into Epi Data version 3.1 and exported to Statistical Package for Social Science (SPSS) version 23.0 for analysis. Frequency, percent, mean, median, and In this study, a total of 671 mother–child pairs (330 (94.60%) employed and 341 (97.70%) unemployed) participated, with a total response rate of 96%. Among the total participants, about 70 (21.2%) [95% CI: ] and 98 (28.8%) [95% CI: ] of children of employed and unemployed mothers, respectively, were stunted. Mothers’ level of education, primary and secondary , monthly family income > 5,000 birr , and children aged between 6 and 23 months  were predictors of stunting among the children of employed mothers. Compared to the mothers who did not receive nutritional education , monthly family income of 2,000 ETB , sex of child (girl)  were predictors of stunting among the children of unemployed mothers. The nutrition intervention should focus on encouraging women’s education as it increases the probability of being employed, improving the income of families by using different income-generating strategies, and strengthening the existing essential nutrition counseling strategy. Likewise, further research work on the difference between employed and unemployed mothers on stunting status is also recommended to researchers. Z-scores of less than 2 SDs of height for age , 37% of under-five children are short for their age or stunted and 12% are severely stunted. The prevalence of stunting generally increases gradually with age, from 22% among children aged 6–8 months old up to 44% of children aged 48–59 months, and it is also slightly higher among boys than in girls (40% vs. 33%)  II target and the Sequota declaration to reduce stunting at the rate of 26% by 2020. Besides, there is a great disparity in stunting rates across regions, residences, and economic status. Hence, stunting remains a public health concern in Ethiopia and more intervention is considered necessary to accelerate learning . InvolviIn addition, there is an agreement that income earned by a mother or maternal employment has a direct effect on childcare, the nutritional status of children, and the mothers themselves . FurtherAlthough previous literature shows that a high risk of stunting is associated with socioeconomic classes , there iThis community-based comparative cross-sectional study was conducted in the Gurage Zone, 158 km away from Addis Ababa, the capital city of Ethiopia, and 345 km from Hawassa, the capital city of the Southern Nation Nationality People’s region (SNNPR). In the district, there are three sub-cities and seven kebeles (which refer to the lower-level administrative divisions) under these sub-cities. It has a total population of 72,929 living within 14,585 households. A total of 11,377 of them were estimated to be under five children, and 9,772 were aged between 6 and 59 months. The study was conducted in May 2021, in the Gregorian calendar.The findings of this survey are projected for all mother—child pair aged 6–59 months in the Gurage Zone, while those children aged 6–59 months from a randomly selected kebele were the study population. Those children aged 6–59 months old who have resided in the study area for at least 6 months and above and who have volunteered to participate in the study were considered as study participants, while those children whose mothers were unable to respond to the interview due to severe illness were excluded. Sample size determination.f  = 7.84, when the power = 80%, and = 5% considering a 10% non-respondent rate and a 1.5 design effect, using a statistical formula.The sample size was determined by considering both objectives; for the first objective, we assumed the prevalence of stunting (P) among children of unemployed and employed mothers was 26.5 and 18.5%, respectively, from previous studies ] see .After that, to select the allocated sample of participants from each kebele, we applied systematic random sampling. The sample frame containing the full list of households with children aged 6–59 months was obtained from the list . When there were two 6–59-month-old children in a household, one was selected randomly by lottery method. When the respondent was not available at the time, the data collectors made about 3 visits.A pretested structured interviewer-administered questionnaire containing variables assessing socio-demographic variables, household economic status, maternal health status, and child health-related factors, was used to collect data from the mother or caregiver of the child. After reviewing relevant literature from prior related studies, the questionnaire was prepared in English and translated to the local language (Amharic), and administered in translated form. The questionnaire was pretested a week before the actual survey in an analogous setting in Butajira town on 5% of the calculated sample size and an amendment of the tool was done based on the result from the pretest. After interviewing the mothers of the selected children, the anthropometric measurement for height/length was measured in accordance with WHO guidelines. A portable stand-meter (SECA) was used to measure older children (older than 2 years) while younger children (less than 2 years) were measured using a calibrated length board. The body parts were in touch with the measuring board in proper anatomical position. The child’s body at the occiput, shoulder blades, buttocks, and heels were in touch with the board and recorded to the nearest 0.1.The dependent variable of this study is stunting. Maternal health and health service-related factors such as antenatal care (ANC) follow-up, nutritional information, child health-related factors such as breastfeeding practice, meal frequency, immunization status, and diarrhea exposure.The questionnaire was pretested and administered in the local language. An adequate number of data collectors and supervisors were employed for actual data collection and trained on how they proceeded, and close supervision was undertaken throughout the process. The completeness and consistency of the collected data were checked on a daily basis.Stunted—Children whose height-for-age Z-score is below minus two standard deviations (-2 SD) from the median of the WHO standard .A caregiver is the most responsible person that provides child care when the mother is out of the home for work. A mother is considered to be an “employed mother” if she reports earning income since the birth of the current eligible child until the data collection period by working either in a government, NGO, public, private sector, or other self-managed income-generating work. A mother is considered “unemployed” if she reports having had no work since the birth of her current eligible child until the data collection period, whether in the government, NGO, public, or private sector, or from other self-managed income-generating work.p-value below 0.20 in bivariate were considered for the final logistic regression model to address all possible confounders. Model fitness was tested by using the Hosmer-Lemeshow goodness-of-fit (0.689 and 0.446) for employed and unemployed, respectively, which were good fits for the data). Crude and adjusted odd ratios with 95% confidence intervals were reported. Independent predictors were declared at a P-value below 0.05.The data were coded and entered into the statistical software Epi Data version 3.1 before being exported to the Statistical Package for Social Science (SPSS) version 23.0 for analysis. The analysis was done; frequency, percent, mean, median, and standard deviation were computed, and presented by using tables and figures. A bivariable and multivariable binary logistic regression analysis was conducted to assess the association between the factors and outcome variables. The variables were checked for normality, and multicollinearity . Factors with a Ethical clearance was obtained from the Institutional Health Research Ethical Review Committee at Wolkite University. An official support letter was submitted to those who are concerned. The study, its purpose, procedure, and duration, the rights of the respondents, and possible risks and benefits of the study were clearly explained to each participant using the local language. At last, written informed consent was obtained from participants before they participated in the study. All COVID-19 pandemic prevention standard precautions were followed, including data confidentiality.This study was undertaken among 671 mothers (330 (94.6%) employed and 341 (97.7%) unemployed) who have children aged 6–59 months in southern Ethiopia, with a total response rate of 96%. The respondents’ average age was 32.1 years (+ 5.8), and the age range was 24–45. A total of 301 (91.2%) employed and 326 (95.6%) unemployed were married; 148 (44.8%) employed and 151 (44.3%) unemployed were Muslim; 130 (39.4%) employed and 145 (42.5%) unemployed were Orthodox; 192 (58.2%) employed and 49 (14.4%) unemployed mothers had attended college or higher; and 208 (63%) and 267 (78.3%) employed and unemployed mothers had family sizes of 4–6. More than half (59%) of the employed mothers had a family income of > 5,000 ETB per month, whereas around two-thirds (68.3%) of the unemployed mothers earn between 2,000 and 5,000 ETB see .Among the total 154 (46.7%) children of employed and 160 (46.9%) children of unemployed mothers, 105 (31.8%) children of employed and 97 (28.4%) children of unemployed mothers were aged 6–23 months, whereas 255 (68.2%) children of employed and 244 (71.6%) children of unemployed mothers were aged 24–59 months. In total, 326 (98.8%) children of employed and 332 (93%) children of unemployed mothers were vaccinated for age. Regarding the feeding patterns of half of the children, 167 (50.6%) and 173 (50.7%) of children of employed and unemployed mothers, respectively, were breastfed eight times per day. In total, 228 (69.1%) and 255 (74.8%) of children of employed and unemployed mothers, respectively, had taken complementary diets three to four times per day.Regarding service utilization during pregnancy, all mothers in both groups have reported that they have gotten ANC services at health facilities at least once. A total of 179 (54.2%) employed and 253 (74.2%) unemployed mothers reported visiting a health facility four or more times during their most recent pregnancy. Concerning nutrition information received during any service delivery time, 246 (74.5%) employed mothers and 284 (83.3%) unemployed mothers reported receiving nutrition information. Regarding delivery service, 322 (97.6%) and 324 (95%) of employed and unemployed mothers, respectively, gave birth at the health facility.Among the total participants, about 70 (21.2%) [95% CI: ] and 98 (28.8%) [95% CI: ] children of employed and unemployed mothers, respectively, were stunted.p-value below 0.2 in the bivariable logistic regression analysis were considered for the multivariable logistic regression model.The association between stunting and factor variables were assessed using a step-wise backward binary logistic regression model. Variables with a p-value ≤ 0.2 and have been a candidate for multivariate logistic regression analysis. In the multivariate analysis, maternal education, maternal age, child age, family income, and frequency of breastfeeding showed a statistically independent significant association with stunting at a p-value < 0.05.In bivariate analysis, the age of mothers, maternal education, husband education, family income, age of the child, frequency of breastfeeding, diarrhea, frequency of ANC visit, and nutrition information were associated with stunting at Children whose mothers attended primary and secondary level education  were 1.8 times more likely to be stunted compared to children whose mothers attend college and above. Children whose mothers’ age ranged between 25 and 29  were 92% protected from stunting compared to children whose mothers’ age ranged between 20 and 24 see . Childrep-value of ≤ 0.2 and 95% CI. Those variables significantly associated (p ≤ 0.2) were considered as a candidate for multivariate analysis to control the potential confounding variable. In the final model, sex of the child, nutrition information, maternal education, and family income had a statistically significant association with stunting at a p-value of < 0.05 and 95% CI ] among children of unemployed mothers who had no exposure to nutrition education compared with those children of unemployed mothers who had received nutrition education. Children of unemployed mothers whose mothers were only able to read and write  were 2.9 times more likely to be stunted compared to children of unemployed mothers whose mothers had attended primary and secondary school. Likewise, children of unemployed mothers whose family monthly income < 2,000 ETB  were nearly three times more likely to be stunted as compared with the children whose family monthly income was greater or equal to 2,000 ETB. And a girl child  is two times more likely to be stunted compared with a boy see .This article quantified and compared the burden of stunting and its predictors among children of employed and unemployed mothers. A considerable proportion of children of employed and unemployed mothers  were stunted, which showed that the prevalence of stunting is slightly higher among children of unemployed mothers. It is consistent with other study findings from Wolayta Sodo, town administration, Southern Ethiopia (18.5 and 26.5%), respectively (14), and Wilayat Zone, Southern Ethiopia, 21.8 and 22.6%, respectively (18). This might be due to socio-demographic/economic/and cultural similarities between these study areas. However, other survey reports from Adama town, central Ethiopia (2017) (28 and 39.5%), respectively (10) show that the possible reason for this difference could be the time gap between the studies, as an intensive intervention in childhood.In this study, we found that children of mothers of lower education levels were nearly 3 times more likely to be stunted compared with those of secondary and above levels. It was relatively consistent with the findings from Adama Town, central Ethiopia (10), Wolayta Zone, southern Ethiopia (18), and Uganda (20). The possible explanation for this may be that as women’s level of education increases their awareness of child nutrition, child care practices, healthcare utilization during illness, and immunization service utilization improves, and that in turn affects children’s nutritional status .In addition, the likelihood of being stunted is lower among children of younger employed mothers . It is consistent with a survey report from Wolayta Sodo southern Ethiopia (18). The possible explanation is at a younger age, the number of family size particularly children is limited which enables the mother to give sufficient time to care for her children compared with late age . On the contrary, as the age of children of employed mother increase the likelihood of being stunted lowers . This was supported by the study conducted in the Wolayta Zone, where the prevalence of stunting was significantly higher in the age group of 6–23 months compared to the older children (14). The possible justification for this may be the intergenerational effect of stunting affects children to be stunted at an early age without intensive intervention.This study finding also showed that as family income increases , the likelihood of children of employed and unemployed mothers being stunted is lessened. This is in line with the study finding from the Wolayta Zone, southern Ethiopia (18). This indicates increasing income increases food security at the household level, thus decreasing stunting. Moreover, children from low-income households had low access to adequate dietary intake in kinds and amounts and also decreased purchasing power of the family, and a shortage of other important materials and utilities .Children of an unemployed mother who had no exposure to nutrition education were 2.5 times more likely to be stunted compared with those children of mothers who had been exposed to nutritional education. This finding is in line with the findings of a previous study . This imThis is the first comparative study carried out at community level in Gurage Zone, The limitation of this study comprises since the study used the data since birth like breastfeeding practice, Vit-A supplementation, and others, which may confront memory lapse , and the Shortage of similar studies limited us to making further comparative discussion.In our study prevalence of stunting was 21.2%, 95% CI:  and 28.8%, 95% CI:  for children of employed and unemployed, respectively. This finding is lower compared with the regional, national, and WHO cut-off point of 40% set for stunting. In this study, maternal education, maternal age, family income, frequency of breastfeeding, and child age had a statistically significant association with stunting among children of employed mothers, whereas nutritional information, maternal education, family income, and sex of the child had a statistically significant association with stunting among children of unemployed mothers, thus nutrition intervention should focus on encouraging women education as it increases the probability of being employed, improving income of family by using different income-generating strategies, and strengthening the existing essential nutrition counseling strategy. Likewise, further research work on the difference between employed and unemployed mothers on stunting status is also recommended to researchers.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical clearance was obtained from the Institutional Health Research Ethical Review Committee, Wolkite University. An official support letter was submitted to those who are concerned. The study, purpose, procedure and duration, rights of the respondents and possible risks and benefits of the study were clearly explained to each participant using the local language. Finally written informed consent was obtained from participants before they participated in the study. The data confidentiality and all COVID-19 pandemic prevention standard precautions were kept.All the authors participated in the design, data analysis, drafting, and revising the manuscript, have agreed on the journal to which the manuscript was submitted, approved the final version to be published, and agreed to be accountable for all aspects of the work.


To summarize the advantages of peritoneal dialysis (PD) catheters without capsular puncture (only one pneumoperitoneum needle) puncture technique conducted by our center.  The study examines the clinical data of PD patients  undergoing pneumoperitoneum needle catheterization from January 2019 to May 2021 in the Department of Nephrology at the First Affiliated Hospital of Hebei North University .  A total of 153 surgical cases were collected. There were 91 males and 62 females. The mean (± standard deviation) age was 56.1 ± 18.6 years, and the mean (± standard deviation) follow-up time was 16.7 ± 8.2 months. The average operation time was 30.33 minutes with a standard deviation of 14.80 minutes. The length of abdominal incision is 2.38 ± 0.42 cm, and the blood loss was about 26.3 ± 9.2 ml, including 2 cases of laparoscopic reposition of drift tube, 0 case of pipe blockage, 3 cases of fluid leakage, 1 case of peritoneal dialysis catheter tunnel infection, 4 cases of outlet infection, 12 occurrences of peritonitis, 121.3 patient months in peritonitis, and 0 times in omentum wrapping without bladder injury, incisional hernia, or intestinal injury.  Relative to open operation, the peritoneal dialysis (PD) catheters with pneumoperitoneum needle puncture technique has the following advantages: simpler operation, shorter operation time, less bleeding, less injury, less complications, and higher safety. Moreover, there are no additional costs compared with open operation. Thus, the technique is recommended for clinical applications. More than 270,000 ESRD patients worldwide have been treated with peritoneal dialysis so far [Peritoneal Dialysis (PD) is one of the most important techniques of renal replacement therapy for end-stage renal disease (ESRD) patients . ESRD, ws so far  has exces so far . PD caths so far . Therefos so far . A largeThere are three types of renal replacement therapy for patients with ESRD, including hemodialysis, peritoneal dialysis, and kidney transplantation. Peritoneal dialysis is safe and effective, simple to operate, does not need to rely on machines, and is not easy to cross infection. Biocompatibility is not easy to appear allergic reaction, small impact on the cardiovascular system, and other advantages. When kidney transplantation is not the first choice for ESRD patients, peritoneal dialysis can be prioritized, especially for patients with heart failure and chronic cardiorenal syndrome, excluding contraindications related to peritoneal dialysis. The key to the successful development of peritoneal dialysis is the establishment of access. At present, there are three methods commonly used to establish access, which are surgical incision, percutaneous puncture, and laparoscopic method. Different catheterization methods have their own advantages and disadvantages.Most patients with ESRD have abnormal cardiac function, and surgical incision catheterization takes a long time. At the same time, pain stimulation during muscle layer separation and purse-string suture can induce heart failure symptoms such as chest tightness, asthma, and gastrointestinal symptoms such as nausea and vomiting. However, the catheterization time of peritoneal dialysis is short, there is no need to separate the muscle layer and involve the peritoneum, the pain and stimulation are small, the patient's tolerance is increased, and the cardiac function is less affected. At the same time, surgical incision catheterization cannot be used as early as possible for peritoneal dialysis treatment, which prolonging the length of hospital stay. In addition, nephrology physicians in primary hospitals do not have the qualification of surgical catheterization and the lack of catheterization technology, which limits the development of peritoneal dialysis.The advantages of peritoneal dialysis catheterization are as follows: no surgical assistance is required; shorten the catheterization time and reduce the surgical wound; relieve pain of patients; abdominal incision and purse-string suture are not required, and the probability of fluid leakage is reduced. The catheter technique has a high survival rate, and peritoneal dialysis can be started immediately. Low complication rate: the hospital stay is shorter and more economical.In recent years, our center has made several improvements on the PD catheterization surgery, where we have achieved better clinical results by using the pneumoperitoneum needle catheterization. This paper details the techniques we have learned.From January 2019 to May 2021, 153 patients with end-stage renal disease who received uncapsulated (only one pneumoperitoneum needle) peritoneal dialysis catheterization in the Department of Nephrology at Hebei North University were selected for the study. All patients included had clear indications for renal replacement therapy, no PD contraindication, and the operation was performed by the same surgeon, and the Tenckhoff straight tube was used. This study was approved by the hospital ethics committee, and all patients were informed and signed informed consent.Patients were given routine skin preparation, enema, bladder emptying, and antibiotics to prevent infection. The pneumoperitoneum needle is shown in The patient was placed in the supine position, and a body surface marking line was drawn at the rectus abdominis muscle 10-12 cm above the pubic symphysis. The skin of the operation field was routinely disinfected, and 1% lidocaine was used for local infiltration anesthesia. The skin incision was about 2 cm, and the subcutaneous tissue was bluntly separated, the anterior sheath of rectus abdominis muscle was cut open, and the rectus abdominis muscle was bluntly separated, and the sheath of rectus abdominis muscle was exposed, as shown in The supine position described above refers to lying on the pillow with the head tilted to one side. Arms at the side of the body, legs naturally straight, and the pillow straight over the head of the bed. Rectus abdominis muscle was located on either side of the midline of the anterior abdominal wall. The rectus abdominis muscle is in the rectus abdominis sheath. It is a band shaped multiabdominal muscle, which is wide above and narrow below, and rises from the pubic symphysis and the pubic crest.① Basic data of patients before operation ; ② perioperative condition: operation time, incision length, intraoperative blood loss, time to start peritoneal dialysis, conversion to laparotomy, hospital stay after operation; ③ visual analogue scale score (VSA) was used to evaluate the pain degree of d0, D1, D2, and D3 after catheterization. ④ Intraoperative and postoperative complications: including PD drift tube, tube blockage, fluid leakage, exit infection, tunnel infection, peritonitis, and organ injury. ⑤ Survival rate of PD catheter technology: the PD tube removal due to complications, inadequate dialysis, peritoneal ultrafiltration, and other reasons from successful PD catheterization to the end of follow-up was observed, and the survival rate of PD catheter technology was calculated.According to their own conditions, patients chose automatic peritoneal dialysis (APD), daytime ambulated peritoneal dialysis (DAAPD), and continuous ambulated peritoneal dialysis (CAPD), and glucose peritoneal dialysis fluid produced by Baxter was used for PD fluid.N/%). The PD catheter survival curve was drawn by Graphpad Pism 5.0.SPSS 21.0 software was used for data statistics, in which the measurement and count data were expressed in the form of (±s) and rate , diabetic nephropathy in 47 patients (30.7%), hypertensive nephropathy in 6 patients (3.9%), polycystic kidney disease in 3 patients (1.9%), and other renal diseases in 13 patients (8.5%). The basic data of the patients are shown in All 153 patients with catheterization completed surgery successfully, and no patient was transferred to laparotomy. Specific details are shown in The patient presented with moderate pain on the day after surgery and basically felt no pain 3 days after surgery. The score is shown in 2 cases of laparoscopic reduction with drift tube occurred after surgery; 3 cases of fluid leakage; peritoneal dialysis catheter tunnel infection: 1 case; 4 cases were infected by export; peritonitis occurred in 12 patients (121.3 patient months). There were no bladder injury, incisional hernia, and intestinal canal injury in all cases see .The follow-up time was up to January 2022; the longest follow-up time was 36 months, with an average follow-up time of 16.7 ± 8.2 months. There were 153 patients with catheter technique failure 3 times; 2 cases were catheter displacement, within 1 week after surgery. One case was peritonitis, which occurred 1 year and 3 months after surgery. The technical survival curve of the catheter is shown in PD is an important alternative therapy for patients with end-stage kidney failure. Due to its advantages such as simple operation, early retention of residual renal function, hemodynamics stability, and low risk of blood disease transmission, , the proAt present, there are three kinds of catheterization commonly used in clinic: open surgical catheterization, laparoscopic catheterization, and percutaneous catheterization. The percutaneous catheterization mainly includes Seldinger technique or Trocar technique. Different types of surgery also have their own advantages and disadvantages. Open surgical catheterization is the standard catheterization method commonly used in clinic . ComparePeritoneal dialysis catheters were placed in our center by PD catheterization without encapsulation (only one pneumoperitoneum needle). Because of the unique structure of the pneumoperitoneum needle, it can penetrate the abdominal cavity smoothly; the puncture feeling is easily sensed and will not damage the intestinal tract. And the pneumoperitoneum needle can be inserted vertically into the postsheath; because of the small opening of the peritoneum and the posterior sheath, no purse-string suture is needed, which can reduce the difficulty of the operation, shorten the operation time, and reduce the amount of bleeding during the operation, causing less pain to the patient. In addition, pneumoperitoneum needle can be fixed firmly in the peritoneal cavity of peritoneal dialysis catheter. The rate of leakage was only1.96%, no greater omentum encapsulation and organ injury, and the rate of peritonitis was 121.3 patient months, which was also lower than that reported in the literature. In addition, from the perspective of health economics, pneumoperitoneum puncture can reduce complications without increasing patient costs, which is especially suitable for primary doctors.In conclusion, pneumoperitoneum needle puncture PD catheterization has the advantages of simple surgical process, short time, less bleeding, less patient injury, high safety, low rate of drifting tube and greater omentum wrapping rate, low infection rate of exit and tunnel, and economic benefits. Meanwhile, PD catheterization is widely applicable to a wide range of people and can be safely applied to emergency and elective peritoneal dialysis patients, which is worthy of clinical promotion.