Mortality and morbidity rates among critically ill septic patients having acute kidney injury (AKI) are very high, considering the total number of deaths after their admission. Inappropriate selection of the type of continuous renal replacement therapy and inadequate therapy become the immediate causes of these issues. Dialysis is a commonly used treatment intended to prolong the life of AKI patients. Dialysis membranes, which are the core of dialysis treatment, must be properly selected to ensure fair treatment to the patients. The accumulation of certain types of molecules must be dealt with using the right membrane. Whether it is low-flux, high-flux, or adsorptive type, the dialysis membrane should be chosen depending on the condition of the patients. The selection of dialysis membranes should also be based on their effect on the treatment outcomes and well-being. All these options are needed to serve the patients of different clinical settings. The use of dialysis membranes is not restricted to conventional haemodialysis, but rather they can be employed in haemoperfusion, haemofiltration, haemodiafiltration, or a combination of any two of them. This review focuses in-depth on different types of dialysis membranes, their characteristics, and approaches in addressing the issues encountered in patients having AKI with sepsis and/or multiorgan failure in intensive care units. Membrane technology is growing rapidly. At the beginning of the use of this technology, membranes were widely applied to support the development of science and technology in theoretical physics and chemistry, rather than for commercial use. Due to various technological benefits, researchers began developing membrane applications for human survival. One of the applications is for kidney disease treatment, namely haemodialysis (HD) through a principle of dialysis, whereby the membrane acts as an artificial kidney. Haemodialysis is not intended to heal the patient but to prolong the life of the patient in acute and chronic conditions. Acute kidney injury (AKI) and acute-on-chronic kidney failure (ACKF) are conditions when the patients experience a sudden negative change in blood quality caused by the accumulation of toxins.Specifically, AKI is a condition in which the concentration of creatinine in serum increases >50% more than its normal concentration in a very short time (<7 days). The urine output becomes less than 0.5 mL/kg/h for more than 6 h. Based on the National Kidney Foundation (NKF) in the USA, around 37 million people have been affected by kidney disease, affecting 15% of the adult population. There are different conditions of AKI, namely prerenal, renal, and postrenal. In prerenal and postrenal conditions, the blood flow to the kidney and the urine flow from the kidney is affected. Meanwhile, the renal condition can be caused by glomerulonephritis, blood clotting, and blood vessel disease, whereby the kidney fails to purify the blood. Patients with AKI and ACKF have to be treated using HD [Acute Dialysis Quality Initiative has classified AKI based on the consensual risk, injury, failure, loss of kidney function, and end-stage kidney disease (RIFLE). The RIFLE classification is based on serum creatinine (sCr) and urine output (UO). Based on the glomerular filtration rate, the risk, injury, and failure are occurring while the sCr increases 1.5, 2, and 3 times, respectively. The patients are defined to have the loss of kidney function and the end-stage kidney disease when their kidney function has been lost for more than 4 weeks and more than 3 months, respectively. Based on the UO, the risk, injury, and failure are classified with less than 0.5 mL/kg/h for 6 h, less than 0.5 mL/kg/h for 12 h, and less than 0.3 mL/kg/h for 24 h or anuria for 12 h, respectively. The RIFLE is used as a guideline to diagnose and justify the patient’s condition for kidney conditions [There are two dialysis treatments for AKI patients, namely intermittent haemodialysis (IHD) and continuous renal replacement therapy (CRRT). The main focus of the dialysis treatments in AKI is to remove excess water and waste. IHD is used for a short period of time 3–4 h), while CRRT is conducted continuously (24 h) for several days. CRRT is applicable for critically ill patients having different catabolic states, systemic inflammatory syndromes with or without sepsis, and other organ failures. CRRT does not cause abrupt variations in fluid removal or osmolality, ensuring good clearance of solute and better haemodynamic tolerance due to the slower liquid flow rate [ h, whileA kidney is a vital organ to clean the body fluid from acidic, organic, and metabolic waste through a series of urine production stages that cover water and toxin clearance. Kidney failure is one of the significant health problems of the world population suffering from the disease. It refers to the incapability of kidneys to perform their essential tasks: eliminating waste products from body metabolisms  and maintaining electrolyte balance in the body. It is commonly caused by certain conditions, such as diseases  and injuries that induce sepsis or systemic inflammatory response syndrome. AKI is a sudden reduction of kidney function within 48 h, indicated by the increasing concentration of creatinine in serum of equal to or more than 0.3 mg/dL, the increasing percentage of creatinine of equal to or more than 50%, or the reduction of excreted urine of less than 0.5 mL/kg per hour for more than 6 h [Haemofiltration (HF), haemodialysis (HD), and haemodiafiltration (HDF) are among the treatment options for chronic kidney failure conditions like AKI and ACKF. The selection of dialysis membrane is very important to achieve adequate treatment. The patients have to be assessed in terms of their quality of blood and the amount of uremic toxins present prior to HD. Failure to choose the suitable dialysis membrane may cause an adverse effect and worsen the patient’s condition.Uremic toxins are defined as the products of metabolism that accumulate in the body and their accumulation is associated with uraemia due to renal degradation and/or impaired excretory capacity. Based on the physicochemical characteristics, uremic toxins are generally divided into three groups: small water-soluble uremic toxins (molecular weight <500 Da), middle molecules , and protein-bound uremic toxins . The accVanholder et al.  stated tSmall water-soluble uremic toxins are easily removed by HD . These u2-microglobulin would induce cardiovascular events, including stroke, myocardial infarction, and heart failure, until cardiovascular mortality in every stage of chronic kidney failure patients. These uremic toxins can be removed using high-flux membrane, adsorptive membrane, or by haemoperfusion. The middle-molecule uremic toxins are dangerous if accumulated in the blood as they may cause endothelial or leukocyte dysfunction and may exert proinflammatory and hepatotoxic effects that contribute to the increase of mortality by destroying six vital organs as kidneys, heart, lungs, liver, brain, and gastrointestinal.The middle molecules can be normally removed by dialysis using high-flux membranes, and the molecules are hardly cleared by conventional dialysis or low-flux membranes . The midThe protein-bound uremic toxins can increase the body’s susceptibility to infection and cardiovascular complications. According to Sakai , there aHaemodialysis is a replacement therapy for kidney failure patients to remove excess metabolic waste or uremic toxins from blood, such as water, sodium, potassium, hydrogen, urea, creatinine, uric acid, and other substances through a semi-permeable membrane, where the processes like diffusion, osmosis, and UF occur without losing the essential substances, such as glucose, electrolytes, and amino acids . The priThere are two compartments in the dialyser to contain blood and dialysate, separated by membranes. Dialysate flows in counter-current to the blood flow on the other side of the membrane to maximise solute concentration gradient for efficient diffusion. Diffusive clearance of a solute depends on its molecular weight and electrical charge, as well as the blood-dialysate concentration gradient, blood and dialysate flow rates, and the membrane characteristics in terms of diffusion coefficient . Small mSince the first creation of HD membrane, this membrane has been derived from polymeric materials. Membrane separation technology is effective because it is flexible, requires little energy, does not alter the molecular structure of the separated substance, can be operated at room temperature, and does not require additional chemical substances during separation . The diaSeveral properties are required for a dialysis membrane, such as high solute permeability, high water permeability, the balance between solute and water permeability, mechanical strength in wet state, satisfactory biocompatibility, and low cost. HD membranes may become wet through contact with blood, where there will be a change in inner diameter, thickness, or length, and the membranes must also have excellent mechanical strength. The best membranes applied in HD are membranes with a large pore area, strong, stretchable, thin, and lightweight .2/m3 compared to a flat sheet membrane with a surface area density of 400 m2/m3. A hollow fibre membrane also has a stronger mechanical structure than a flat sheet membrane. However, to produce a good membrane, the hollow fibre must be thin with a very small diameter (about 200 nm) so that more toxins in the body can be eliminated from human blood [In general, membranes used for HD application are hollow fibre rather than flat sheet membranes. This is due to many drawbacks of a flat sheet membrane, such as frequent fouling, resulting in reduced membrane performance. In addition, the membrane also has a relatively small surface area when applied in HD. Compared to the flat sheet membrane, a hollow fibre membrane offers several advantages for HD. The performance of hollow fibre membrane is better due to its higher total surface area . The suran blood .A cellulose-based membrane without modification was used in the earlier development of HD membrane. This membrane is homogeneous, symmetric, and has good performance for small water-soluble molecules. In the 1970s, a synthetic membrane dialyser was developed with higher water permeability for the purpose of blood filtration. The most noticeable changes of this development are larger pore size, a thicker wall structure, higher hydrophobicity, more uniform pore size and distribution, and a more asymmetric membrane structure. Those changes influenced the performance of HD membranes to become better and more stable over a longer period . VariousHoenich  reviewedMeanwhile, PSf as a membrane is advantageous due to its high chemical resistance and is also not reactive in mineral acids, alkalis, and salts. Furthermore, PSf has excellent resistance over a wide temperature range (75–125 °C) and pH range (1–13). The main drawback is its higher fouling tendency than hydrophilic membranes . TherefoBlending polymers is interpreted as a physical mixture that is not covalently bonded by accumulating the properties of different polymers into a single membrane . This teResearchers have carried out the blending of hydrophobic polymers like PSf and PES using a hydrophilic polymer like polyvinylpyrrolidone (PVP) ,21. A cop-cresol. In addition, zeolite can be used and added to the HD membrane to clear middle-molecule toxins [Biomaterials or biological compounds are also added to HD membranes as additives to increase membrane biocompatibility. Heparin  and vitae toxins .Recently, inorganic nanoparticles like carbon nanoparticles (carbon nanotube and graphene) and metal oxide nanoparticles (titanium dioxide and iron oxide) were used as nanofillers in HD membranes ,29. Nano2-microglobulin) clearance of >20 mL/min. On the other hand, membrane efficiency is determined based on the mass transfer area coefficient of urea, ureaKoA. Membrane with KoA < 500 mL/min is called a low-efficiency membrane, whereas the one with KoA > 600 mL/min is known as a high-efficiency membrane. Although there are specific values to dictate which one is a high- or low-flux membrane, and whether it has high or low efficiency, membranologists often describe the flux and efficiency of the membranes in different terms . Therefore, one could only tell which category the membrane belongs to based on the comparison with various developed membranes reported in research articles.Similar to dialyzers, membranes can be categorised based on their flux and efficiency. A low-flux membrane is termed as having a UF coefficient of <10 mL/h/mmHg, whereas a high-flux membrane is a membrane with a UF coefficient of >20 mL/h/mmHg with middle-molecule  is used to replace the lost plasma filtrate.Another concern is the susceptibility of essential proteins  to be removed due to the high-pressure gradient. Thus, the chosen membrane must possess a well-compromised flux (UF coefficient) to attain the intended selectivity. A slow and continuous HF or HDF is usually performed on patients with AKI . AlthougAdsorption can be categorised as either chemisorption or physisorption. Bonding in chemisorption is stronger than physisorption as chemisorption is simply a chemical reaction with interactions between adsorbates and chemical bonding groups on the surface of adsorbents. In contrast, physisorption involves electrostatic interactions between adsorbates and the surface of adsorbents. Generally, the time needed to reach adsorption equilibrium is shorter for physisorption compared to chemisorption.p-cresol as protein-bounded uremic toxins both with and without modification [In HD, adsorption has been proposed as one of the alternative methods to eliminate uremic toxins, and most studies used adsorptive membranes to remove protein-bound toxins, which are hardly removed via diffusion and UF. Zeolite Y successfully removed fication . Inspirefication . Hence, 2·h·bar) compared to that of the single-layer MMM (1800 350 L/m2·h·bar). The MMMs adsorbed 29 mg/g of AC at an equilibrium concentration of 0.05 mg/mL. When tested towards human plasma for 4 h, the MMMs were able to remove more than 80% of creatinine and para-aminohippuric acid, which is a protein-bound toxin.Tijink et al.  establisp-cresyl sulphate (pCS)). The water permeability of the MMM was 58.4 350 L/m2·h·bar. Compared to the previous dual-layer flat sheet membrane, the dual-layer hollow fibre MMM developed in this study achieved a higher adsorption capacity of creatinine (100 mg/g of AC) at the equilibrium concentration of 0.05 mg/mL. The maximum adsorption capacity of creatinine, HA, and IS was 3064, 134, and 350 mg/g of AC, respectively. In the human blood plasma adsorption study, the MMM maintained 83% removal of creatinine, and it adsorbed 60% pCS, 90% IS, and 95% HA after 4 h of incubation. In the presence of albumin, IS and pCS were poorly removed by adsorption and diffusion even after 6 h of operation. In contrast, the amount adsorbed was higher for all protein-bound toxins during the convection experiment due to the pressure difference. Despite the better performance, albumin partially passed through the membrane during the convection experiment.A year after, Tijink et al.  used the2 and the removal of IS and pCS was 30% and 125% better in comparison to the first generation MMM and up to 100% as compared to particle-free industrial membranes [2/h/mmHg) and a molecular weight-cut off around 12 kDa prevented albumin leakage while achieving excellent removal of protein-bound toxins.In 2016, another attempt was made by Pavlenko et al. . They deembranes . It was Other previously used adsorbents in the membrane include hydroxy appetite (HAP). Although its application in HD is yet to be seen, HAP has good adsorption to protein and is usually used in the medical field due to its biocompatibility and bioactivity . HAP can2/g. The adsorbents are also defined as microporous (pore size < 20 Å), mesoporous (pore size between 20 and 500 Å), and macroporous (pore size > 500 Å). The sorbents must have high selectivity and good transport properties to catch up with the targeted analyte fast.Haemoperfusion is the adsorption of molecules onto the surface of a biocompatible adsorbent via direct contact in an extracorporeal circuit, as opposed to removing toxins and excess body fluids through a semi-permeable membrane . The sorThe US Food and Drugs Administration (FDA) has classified the haemoperfusion system into two classes of medical device: class II and class III. A device is considered a class II medical device when it is used for treating poison and drug overdoses. In contrast, a class III medical device is used to treat patients with liver deficiencies, such as in hepatic coma . Based oThe development of haemoperfusion for HD was continued using zeolites in adsorbing creatinine  and IS (representing the protein-bound uremic toxins). It was reported that 0.025 g of 940-zeolite powders could eliminate 91% of 2 μmol creatinine in 5 min. Meanwhile, PES/zeolite membrane could adsorb 4948 μg creatinine per g membrane and 550 μg IS per g membrane. The adsorption mechanism was proposed to be via electrostatic attraction [The presence of cytokines and endotoxins in the bloodstreams of patients with AKI and sepsis poses a threat to the patients’ life. In the development of haemoperfusion for HD, the researchers in  examinedIn recent years, a well-established sorption cartridge, namely CytoSorb  is integrated with dialysis machines with the intent to adsorb cytokines. It is designed specifically to treat patients with sepsis. This new technology has shown excellent removal of a wide range of crucial cytokines that cannot be eliminated using existing blood purification processes . The carA multicentre study conducted by Basu et al.  on 43 paAnother way to remove cytokines is using specific HD membranes. Due to the huge size of cytokines as part of middle molecules, high cut-off membranes with a larger pore size (>0.01 µm) are used . These mOn the other hand, an increased level of endotoxins is usually observed in patients with AKI. Among the patients, endotoxins are found circulating in the bloodstream after encountering severe traumas. After a few times undergoing dialysis treatment, endotoxins originated from bacterial lipopolysaccharides  found in the dialysate may accumulate in the blood due to their diffusion into the blood during the treatment. This would elevate the level of endotoxins in the patient’s blood. To remove the circulating endotoxins from the patient’s blood, Toray Medical Co. Ltd.  has developed Toraymyxin, a polymyxin B-immobilised fibre blood purification column. The product was approved by the Japanese National Health Insurance system to treat endotoxemia and septic shock. Polymyxin B is known for its bactericidal effect against Gram-negative bacteria. Besides, it can inhibit the effects of endotoxins via binding with the active site (lipid A domain) of the endotoxin molecules. For selective adsorption of endotoxins, polymyxin B is immobilised on the surface of polymeric fibres (membrane). Mortality risk studies on various targeted groups revealed that the use of Toraymyxin significantly reduced the mortality risk ratio .Due to the serious threats imposed by cytokines and endotoxins, the focus is now on developing HD membranes that could remove these two types of molecules simultaneously from blood. oXiris membrane was developed recently, which comprised of AN69 membrane, surface-treated with polyethylenimine, and grafted with heparin on the inner membrane surface. AN69 membrane alone can remove large molecular weight molecules, including cytokines and uremic toxins, by membrane binding . To tackTo date, oXiris is the only membrane  with great removal of both endotoxins (68%) and cytokines (>90%) . This mehdf is the coefficient of haemodiafiltration; Kuf is the coefficient of UF; Kd is the coefficient of diffusion; Quf is UF flow rate; Co is concentration out; Ci is concentration in;  is one chamber only; ( + ) is one dialyzer with two chambers.Ghezi et al.  studied Based on the above mathematical reasoning, two processes that occur simultaneously in a single dialyser are less efficient compared to when they occur in different dialysers. Based on this explanation, a combination of HD and haemoperfusion  as a funThe combination of diffusion, UF, and adsorption using HD and haemoperfusion techniques could offer many advantages. Firstly, the fouling or blocking of pores in membrane surfaces can be avoided . SecondlBased on the description above, dialysis treatments can be divided based on the principle and their capability to remove uremic toxins, as shown in Improper selection of dialysis membranes and the modes of dialysis would result in the inadequacy of blood purification treatment, which will be very detrimental to the patients with AKI and can lead to death. The top priority of choosing a dialysis membrane must be based on its capacity to remove targeted groups of molecules according to the clinical profile of an individual rather than the cost of treatment so that an efficient blood purification process can be achieved. A low-flux membrane, for example, is sufficient to remove small water-soluble molecules over a long period of time for septic patients with unstable haemodynamic conditions. In a high concentration of middle molecules in the blood, a high-flux membrane is needed. High-flux membranes are more versatile as they can be utilised in HD, HF, and HDF modes.On the other hand, adsorptive membranes have been developed to improve the removal of protein-bound uremic toxins and different types of molecules, including cytokines and endotoxins, through diffusion and adsorption. As an alternative, haemoperfusion treatment using a sorbent cartridge is performed to eliminate these recalcitrant molecules due to its higher efficiency compared to HD using an adsorptive membrane. The removal of cytokines and endotoxins from blood, either by adsorptive membrane or adsorbent, is very beneficial in improving the clinical outcomes of septic patients with AKI. In some cases, the integration of haemoperfusion and HD is made to systematically remove all types of uremic toxins at one time.


The results further found that this association was moderated by the type of attitude and larger effect sizes were shown in self-efficacy than in interest, societal relevance of attitude toward science, and mixed attitude. Moreover, the effect sizes of studies with unstandardized measure to assess science achievement were larger than those with standardized measure. Possible explanations for these findings and its implications for future research directions were also discussed in this review.Science education is attracting increasing attention and many researchers focus on the issue about the attitude-achievement relationship in science, but there is still no consistent conclusion. By using a three-level meta-analytic approach, the aim of the current study was to investigate the relationship between attitude toward science and academic achievement in learning science among primary and secondary school students, and to explore if some study characteristics could have contributed to the inconsistent findings with regard to this relationship as observed in the research literature. A total of 37 studies with 132 effect sizes involving a total of 1,042,537 participants were identified. The meta-analytic results revealed that there was an overall positive and moderate relationship between attitude toward science and learning achievement in science ( Science education is an important subject area of study for students, as it is closely tied to a society's economic development. In addition to students' achievement in learning science, affective outcomes related to science learning are also of concern for educators. Over the years, science education educators and researchers have been interested in understanding the relationship between students' attitude toward science and their achievement in learning science  was shown. Likewise, Rennie and Punch (r = 0.66).Over the past decades, after the last synthesis on the students' attitude -achievement relationships Willson, , there hnd Punch  documentr = 0.11), but the relationship between students' engineering attitude (interest in computer design) and performance was negative (r = −0.11).On the other hand, however, there were other studies showing that the relationship between students' attitude toward science and their science achievement was either quite weak, statistically non-significant, or even negative . In this section, we consider some possibilities in this regard.Publication type is a common moderator variable in meta-analysis that captures different types of research publications such as journal article, conference paper, or dissertation. In general, journal articles and some conference papers are peer-reviewed, whereas dissertations are not. Given the belief that studies with statistically significant findings are more likely to be published than those with statistically non-significant findings . In addition, previous research indicated that there were regional differences in science achievement . We contacted the authors that did not report these correlations in their articles to request this information, and studies with no response were excluded.3. A study must report the zero-order correlation between science attitude and academic outcome in science, or reported quantitative data in sufficient detail to allow us to obtain this relationship as an effect size  publication year (year as a continuous variable); (b) publication type ; (c) grade ; (d) geographical region (two categories: Eastern countries and Western countries); (e) type of attitude ; (f) measures of achievement (two categories: standardized and unstandardized). In addition, the first and the second author coded 10% of the randomly selected articles and all disagreements were solved after reading the articles and discussion with the research team. Then, all primary studies were coded independently by two authors with high inter-rater reliability. The intra-class correlation coefficients of each moderator variable were respectively: publication year (ICC = 0.94), publication type (ICC = 1), grade level (ICC = 0.97), geographical region (ICC = 1), type of attitude (ICC = 0.89), and measures of achievement (ICC = 0.86).r between attitude toward science and academic achievement in science from the primary studies were treated as effect sizes in the present meta-analysis. Before conducting the meta-analysis, all correlation coefficients were converted to Fisher's z-scores, because the sampling distribution of r is skewed  is the known sampling variance in the ith effect size in the jth study, κj is the average effect in the jth study, β0 is the average population effect, and VarQ statistic , and I2 statistic . All analyses were performed by using Viechtbauer, metafor package in R version 3.5.1.The  Cheung, . In the  Cheung, . The maxp-values in these tests were >0.05, indicating that there is no enough evidence to suggest publication bias was presented.Publication bias should be taken into account in conducting meta-analysis. Generally, studies with statistically significant results could be more likely to be published, thus included in a meta-analysis, than those with statistically non-significant results, and this was referred to as the “file-drawer problem” , dissertation (18 effect sizes); Grade: elementary school students (13 effect sizes), middle school students (79 effect sizes), high school students (29 effect sizes), others (9 effect sizes); Geographical region: Eastern (42 effect sizes), Western (86 effect sizes); Type of attitude: interest (43 effect sizes), self-efficacy (43 effect sizes), societal relevance (30 effect sizes), mixed (16 effect sizes); Measures of achievement: standardized (70 effect sizes), unstandardized (62 effect sizes). In addition, the 37 included studies involved a cumulative total of 1,042,537 participants, with sample size for individual studies ranging from 21 to 537,170.The present meta-analysis included 37 primary studies containing 48 independent samples and 132 effect sizes, and these studies were published from 1982 to 2020 see . More spr = 0.248 (p < 0.001), was obtained. It indicated that the relationship between attitude toward science and achievement in science of students was positive and moderate. The Q statistic was statistically significant , suggesting that the effect sizes across the studies were heterogeneous. Moreover, the results of the likelihood-ratio tests revealed that the variances within-studies  and variances between studies  were significant. In terms of the total effect size variance, the level 1, level 2 and level 3 accounted for 1.928, 44.617, and 53.456%, respectively. Taken together, moderator analyses are warranted to further explore how study features might have contributed to the inconsistencies of the effect sizes across the studies.The overall analysis results of the association between attitude toward science and achievement in science are shown in p = 0.246) and Begg's correlation test (p = 0.595) also does not show enough evidence to justify the presence of a publication bias. In addition, the fail-safe N was calculated to be 518503, which is much larger than the criteria that 5k + 10 = 5 × 132 + 10 = 670. Overall, all of the assessment results indicated the absence of publication bias in this study.To evaluate the potential publication bias, both funnel plot, the multilevel extension of Egger's regression test, Begg's correlation test, and “fail-safe N” method, as proposed by Fernández-Castilla et al. , were usThe results of the moderator analyses on the association between attitude toward science and science performance are presented in F = 3.983, p < 0.05] and the effect sizes of journal articles (r = 0.260) appeared to be larger than those from dissertations (r = 0.122).There were a total of 132 effect sizes in this study, with 114 from journal articles and 18 from dissertations. We found a statistically significant amount of explained effect-size heterogeneity for the publication type moderator , suggesting that attitude toward science among elementary school students, middle school students, high school students and others was all positively related to their science achievement with some consistency .No significant differences were observed when considering the moderator effect of grade . Studies with samples from Eastern countries had the mean effect size of 0.246, and 0.236 for Western countries.In line with the grade, the geographical region did not explain a statistically significant amount of effect-size heterogeneity . More specifically, the strength of the correlation between science performance and self-efficacy about science (r = 0.314) was stronger than that of interest (r = 0.205), societal relevance of attitude toward science (r = 0.167), and mixed attitude (r = 0.286).We found a significant moderating effect of attitude types . The effect sizes of studies with unstandardized measure were larger (r = 0.304) than those with standardized measure (r = 0.211).There are various instruments to measure achievement. We mainly divided the instrument types into two groups: standardized test and unstandardized assessment. The effect of the moderator was significant [p = 0.151), indicating that the magnitude of effect sizes remained stable over the time period.Studies included in our meta-analysis were published from 1982 to 2020 and there was a long time span. Our analysis showed that the association between attitude toward science and academic achievement in science did not appear to have changed with the time, with the slop of this regression model being statistically non-significant  could have contributed to some observed inconsistent findings about this relationship across the studies.Our investigation showed that, across the studies conducted over the past several decades, the overall correlation between attitude toward science and academic achievement in science was 0.248, a moderate positive association. Similar findings had been found in previous empirical studies  were examined for their possible contributions to the inconsistent findings across individual studies. Finally, publication type, the type of attitude, and measures of achievement were shown to have moderating effects on the effect sizes of the studies. These findings, or lack thereof, were discussed below.Our analysis found that the average effect size from journal articles was larger than that from dissertations. This may be due to the small number of dissertations (only five articles) in the included studies. However, based on the fact that our previous results did not show enough evidence to justify the presence of publication bias, this finding should be interpreted with caution.Our synthesis showed that there was no significant difference among students at different grade levels , and science attitude had a moderate positive relationship with science learning in these grade levels. An issue that students' s attitudes toward science might decline from elementary to middle school is received with concern . This result was in agreement with some other research showed that the general relationship between attitude toward science and knowledge of scientific facts varied little across different countries  could be beneficial in a long term . There could be other factors  that could affect the attitude toward science and science learning . Nissen  showed tThe original contributions presented in the study are included in the article/ZC led the study design, data collection, statistical analysis, and drafted the manuscript. PM helped to analyze the data and draft the manuscript. XC and JH helped to design the study and collect data. XF helped to draft the manuscript. All authors read and approved the final manuscript.This research was supported by the National Natural Science Foundation of China (Grant No. 62107018), Grant CCNU20QN025 from the Fundamental Research Funds for the Central Universities, and CCNU19TD019 from the self-determined research funds of CCNU from the colleges' basic research and operation of MOE.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.


Intensity modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT) has become the standard treatment for patients with high-risk prostate cancer. Two techniques of rotational IMRT are commonly used in this indication: Volumetric Modulated Arc Therapy (VMAT) and helical tomotherapy (HT). To the best of our knowledge, no study has compared their related costs and clinical effectiveness and/or toxicity in prostate cancer. We aimed to assess differences in costs and toxicity between VMAT and HT in patients with high-risk prostate cancer with pelvic irradiation.We used data from the “RCMI pelvis” prospective multicenter study (NCT01325961) including 155 patients. We used a micro-costing methodology to identify cost differences between VMAT and HT. To assess the effects of the two techniques on total actual costs per patient and on toxicity we used stabilized inverse probability of treatment weighting.The mean total cost for HT, €2019 3,069  was significantly higher than the mean cost for VMAT €2019 2,544  (p <.0001). The mean ± SD labor and accelerator cost for HT was €2880 (± 583) and €1978 (± 475) for VMAT, with 81 and 76% for accelerator, respectively. Acute GI and GU toxicity were more frequent in VMAT than in HT . Late toxicity no longer differed between the two groups up to 24 months after completion of treatment.Use of VMAT was associated with lower costs for IMRT planning and treatment than HT. Similar stabilized long-term toxicity was reported in both groups after higher acute GI and GU toxicity in VMAT. The estimates provided can benefit future modeling work like cost-effectiveness analysis. The fSeveral studies have suggested more favorable dosimetric parameters with VMAT when compared with step-and-shoot or conventional IMRT in patients with prostate cancers, including high-risk prostate cancers –12. VMATWhen comparing VMAT techniques and helical tomotherapy (HT) only small significant dosimetric differences in prostate cancer were observed  includinAmong attempts to estimate costs and effectiveness associated with these advanced technologies, we retrieved only one in prostate cancer that compared VMAT to IMRT and found it “cost-effective” . In a reTo the best of our knowledge, no study has compared costs and clinical effectiveness and/or toxicity of VMAT versus HT in prostate cancer. Only two studies , 20 from® Elekta, as done in the literature, since this is the same VMAT technology developed by two manufacturers. We referred to them both as VMAT, when appropriate.The present study aimed to assess differences in costs and toxicity between VMAT and helical tomotherapy in patients with high-risk prostate cancer. For this study, we considered no differences between VMAT RapidArc™ and VMATso called in French “RCMI pelvis”), which aimed to compare costs and clinical outcomes of IMRT with VMAT (Rapid’Arc™ and VMAT® Elekta) versus helical tomotherapy (HT) (Tomotherapy®) in prostate, cervical, and anal canal cancers, with pelvic lymph node irradiation . The “RCMI pelvis” study had the same protocol as the ‘ART-ORL’ study on head and neck cancer, and both studies were carried out jointly by fourteen French academic cancer centers  divided by the number of workable yearly hours. We estimated the full gross wage on a 15-year experience basis and on a collective labor agreement of UNICANCER, a consortium of the 18 French cancer centers. For all cost estimates, we used the same method as described in Perrier et al. , except Where Nhs = annual number of dedicated hours, and labor = medical physicist or biomedical technician.We obtained data on capital resources, such as equipment  from standardized questionnaires, as previously described . EquipmeWe estimated total actual costs per patient that vary between VMAT and HT from the hospital perspective. All estimates were in Euro 2019, all taxes included, but without discounting as the analytic time horizon for costs was less than 3 months. It is worth noting that we could not estimate the resources used for treatments associated with acute toxicity, since all treatment types, but hospitalization, were not collected in the frame of the study.We analyzed acute toxicity (≤3 months) and late toxicity , thWe described patients’ characteristics using mean and standard deviation (SD) for continuous variables, or count and percentage for categorical variables. In addition, we assessed differences between treatment groups, from the original datasets, using logistic regression, and multinomial logistic regression for binary variables and tumor stage (cT) respectively, and linear regression for continuous variables. We compared differences in hours spent for treatment, QC, and internal maintenance between the two techniques using a non-parametric Wilcoxon test and we used a paired Wilcoxon test for comparing differences in duration of treatment session. We tested uncertainty on the total cost of each technique by running a one-way sensitivity analysis over the range of plausible parameters and illustrating with a Tornado plot showing the impact of increasing and decreasing each of the parameters by 20%, a range suggested in the methods of sensitivity analysis in economic evaluation . In addiSimilarly to Bibault et al. , we usedTo assess the impact of the two techniques on total costs and toxicity we ran linear regressions (costs) and ordered logistic regressions (toxicity) adjusting for sequential versus SIB plans. All regressions were performed before and after having introduced IPTW.https://CRAN.R-project.org/package=stddiff) to compute the standardized differences for all categorical variables with more than two levels.We performed all analyses using R software version 3.6.1. We used the stdidff package . After IPTW, we observed almost no differences between the VMAT and HT groups Table 1.We observed similar median annual treatment times (Interquartile range—IQR) spent with VMAT and helical tomotherapy (HT), with 2,513 h  and 2,520 h , respectively (P = .7). In addition, we did not find any statistical differences in median annual time spent for quality control and internal preventive maintenance, 194.5 h  were spent with VMAT and 144 h  with HT (p = .28). We found that the median time for the first session was 18 min per patient for HT and 20 min for VMAT (p = .31) , with €2,659  versus €2,498  for VMAT, and €3,902  versus €2,895  for helical tomotherapy. The variation was mainly due to the irradiation phase, where accelerator immobilization time and labor time were more expensive in the sequential process than in the SIB process , whatever the machine Table 3BThere was no difference in serious adverse event related hospitalization, nor any permanent discontinuation of treatment reported in the study. In acute toxicity, we observed only one hospitalization due to dysuria in the HT group. In late toxicity, three hospitalizations were noted for dysuria on stenosis, hematuria, and rectal bleeding on radiation proctitis in the VMAT group and one for rectal bleeding on radiation proctitis in the HT group.The analysis based on the “RCMI pelvis” prospective multicenter study found that each hospital spent on average an additional €525 per patient when they used helical tomotherapy (HT) rather than VMAT for IMRT preparation and delivery in high-risk prostate cancer patients with pelvic lymph node irradiation. Considering health outcomes, although acute GI and GU toxicity were significantly higher for VMAT than for HT, the late toxicity outcomes (up to 24 months after completion of treatment) no longer differed between the two groups.The economic results are consistent with the data on head and neck cancers published by Perrier et al., which show an excess in mean costs for HT over VMAT . In the In our micro-costing study, we were able to refer to the Diagnosis-Related Group (DRG) related tariff for a given procedure, and that the national health insurance system (NHIS) reimburses hospitals. As reported in a recent European study, a higher reimbursement is made in France for treatments with helical tomotherapy when comparing to other VMAT machines . The curIn terms of toxicity, comparative evidence between VMAT and helical tomotherapy is limited. Our study found significant higher frequency in acute GI and GU in VMAT than in HT, but no worse significant outcomes in late toxicity. Our results are similar to those of Bibault et al. in head and neck cancers , who aftThis study used rigorous methods to assess the costs and toxicity associated with helical tomotherapy (HT) and VMAT IMRT in prostate cancers. The large variation in baseline characteristics between the two techniques demonstrated the importance of using the propensity score as it makes appropriate adjustment possible for reducing confounding bias when estimating treatment effects. In the economic analysis of radiotherapy, micro-costing represents an accurate method for collecting details of the resources used for costing procedures. To our knowledge, this study is the first of its kind to estimate the costs and toxicity of VMAT and HT in high-risk prostate cancers with pelvic lymph node irradiation with long follow-up time. The identification of treatment delivery as a major cost driver and source of difference between the techniques used is a result of particular interest, given cancer centers’ efforts to introduce new radiotherapy techniques. Applying micro-costing methodology contributes to a broader European (EU) effort to improve knowledge of the resources allocated to radiotherapy within the overall resources for treating cancer patients , 40–43, This study has certain limitations. The first relate to the data collection. Collecting data in real-world clinical practice has some advantages, but it can also be challenging on both the clinical and the funding sides. This has resulted in variability in patients recruited across cancer centers and in a small population sample. In addition, randomization between treatment groups was not possible. We note that the propensity scores we used do not account for the effect of unmeasured covariates , 45. BecAssessing the effectiveness and value associated with the IMRT treatment of prostate cancer with pelvic lymph node irradiation is of particular importance. The study found evidence to support the hypothesis of cost differences between VMAT and HT for IMRT preparation and delivery in favor of VMAT, and no toxicity differences in the long term after more acute GI and GU toxicity for VMAT than for HT. Our findings have already the potential to help clinicians’ decision-making. For the payer, the French NIHS, these findings support an increase in the DRG reimbursement of a VMAT session. Our approach paved the way to a cost-effectiveness model that will combine the long-term health impacts of the two techniques, already identified, to the quality of life reported by patients to be assessed along with long-term costs of VMAT and HT.The data that support the findings of this study are available on request from the last author (SS).The study was approved by the National Ethics Committee  and the National Committee for protection of personal data (DR-2011-277 N°911317). The patients/participants provided their written informed consent to participate in this study.Conceptualization, M-AM and GP. Methodology, IM, MB, GP, CG-C, and SS. Software, MB and CG-C. Validation, IM, MB, GP, CG-C, and SS. Formal analysis, IM, MB, GP, and SS. Investigation, DA, PP, NM-N, PG, DP, BC, PD, NS, GN, JK, IL, and SS. Resources, IM, MB, and GP. Data curation, IM, GP, and CG-C. Writing—Original draft preparation, IM, MB, and SS. Writing—Review and editing, IM, MB, and SS. Visualization, IM, MB, and SS. Supervision, MB and SS. Project administration, GP. Funding acquisition, M-AM. All authors contributed to the article and approved the submitted version.The three manufacturers  financially supported the RCMI pelvis study. However, the RCMI pelvis is an independent study and the ideas and opinions expressed in this work are those of the authors and do not necessarily represent those of the manufacturers. The funders  had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.DA declares conflict of interest with Novagray, which has nothing to do with this study.The remaining 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.


The relationship between three scoring systems  and in-hospital mortality of intensive care patients with ST segment elevation myocardial infarction (STEMI) is currently inconclusive. The baseline data, LODS score, OASIS score, SAPS II score, and in-hospital prognosis of intensive care patients with STEMI were retrieved from the Medical Information Mart for Intensive Care IV database. Propensity score matching analysis was performed to reduce bias. Receiver operating characteristic curves (ROC) were drawn for the three scoring systems, and comparisons between the areas under the ROC curves (AUC) were conducted. Decision curve analysis (DCA) was performed to determine the net benefits of the three scoring systems. LODS and SAPS II were independent risk factors for in-hospital mortality. For the study cohort, the AUCs of LODS, OASIS, SAPS II were 0.867, 0.827, and 0.894; after PSM, the AUCs of LODS, OASIS, SAPS II were 0.877, 0.821, and 0.881. A stratified analysis of the patients who underwent percutaneous coronary intervention/coronary artery bypass grafting (PCI/CABG) or not was conducted. In the PCI/CABG group, the AUCs of LODS, OASIS, SAPS II were 0.853, 0.825, and 0.867, while in the non-PCI/CABG group, the AUCs of LODS, OASIS, SAPS II were 0.857, 0.804, and 0.897. The results of the Z test suggest that the predictive value of LODS and SAPS II was not statistically different, but both were higher than OASIS. According to the DCA, the net clinical benefit of LODS was the greatest. LODS and SAPS II have excellent predictive value, and in most cases, both were higher than OASIS. With a more concise composition and greater clinical benefit, LODS may be a better predictor of in-hospital mortality for intensive care patients with STEMI. In the past decade, the widespread use of percutaneous coronary intervention (PCI) has significantly increased the survival chances of STEMI patients3, however, the survival rate is still not within the ideal range. According to reports from recent studies5, the residual in-hospital mortality of STEMI ranges from 5–10%. Risk classification is critical for STEMI and can be used for selecting treatment regimens as well as planning hospital discharge, especially for patients admitted to the intensive care unit (ICU). But currently, there is no recognized tool for predicting in-hospital mortality for intensive care patients with STEMI. Thus, it is particularly important to find an effective tool.Acute myocardial infarction (AMI) is one of the leading causes of global cardiovascular burden, among which ST elevation myocardial infarction (STEMI) has attracted much attention of clinicians due to its high mortality and morbidity6. The LODS score has been effectively used to predict the mortality of intensive care patients with sepsis and patients in neurological ICU8. The Oxford Acute Severity of Illness Score (OASIS) was proposed in 2013 by machine-learning algorithms, and predictive models of ICU mortality using OASIS achieved an area under the receiver operating characteristic curve of 0.88 and calibrated well9. The Simplified Acute Physiology Score (SAPS II) provides an estimate of the risk of mortality without having to specify a primary diagnosis and was regarded as a starting point for evaluation of the efficiency of ICU10. In this study, we aimed to explore the performance of the above three scoring systems in predicting the in-hospital mortality of intensive care patients with STEMI, to provide valuable clues to clinical practice.Several scoring systems have been proven effective for predicting mortality in intensive care patients. The Logistic Organ Dysfunction System (LODS) is an organ dysfunction scoring system and permits the calculation of predicted mortality based on the organ dysfunction score on the day of ICU admissionhttps://mimic.mit.edu/). The database contains real hospital stays between 2008 and 2019 for patients admitted to a tertiary academic medical center in Boston, MA, USA. According to the official requirements of the database, investigators must complete the "Protect Human Research Participants" exam on the National Institutes of Health website and sign a data use agreement before granting access11. One author (Tianyang Hu) passed the exam (record ID: 37474354) and obtained access to the database.This retrospective study was designed based on the critical care database, Medical Information Mart for Intensive Care IV , and scoring systems . PCI is the standard interventional treatment modality for patients with STEMI12, also was proved to be effective on one-year mortality in non-ST-segment elevation myocardial infarction (NSTEMI) patients13. Approximately 20–30% of patients are not eligible for PCI and require surgical intervention, that is, coronary artery bypass grafting (CABG)15. Therefore, we additionally investigated whether the included patients underwent PCI or CABG.All intensive care patients diagnosed with STEMI were screened and identified by the “long_title” in the “d_icd_diagnoses” table of MIMIC-IV database. Since one patient may be admitted to the ICU multiple times, we only included the first ICU stay for each patient. Navicat Premium software (v15.0) was used to extract the following data of the included patients from MIMIC-IV database (v1.0): age, gender, length of ICU stay, length of hospital stay, coexisting comorbidities , laboratory tests , vital signs  of the receiver operating characteristic curves (ROC).The Kolmogorov–Smirnov test was used to assess the normality of continuous variables. Normally distributed variables were expressed as mean ± standard deviation (M ± SD), and the independent sample t-test was used for comparison; if the distribution was abnormal, continuous variables were expressed as the median with interquartile range (IQR), and Wilcoxon rank-sum test was used for comparison. Categorical variables were expressed as numbers and percentages and compared using the Chi-square test. Binomial logistic regression analysis of the three scoring systems for in-hospital mortality in intensive care patients with STEMI was conducted to adjust the results of the statistical analysis for potential confounding factors by selecting appropriate variables closely related to the condition of STEMI. Variables with Propensity score matching (PSM) analysis was performed to reduce bias between the in-hospital death group and survival group based on the following variables: age, gender, length of hospital stay, and underwent PCI/CABG or not. The propensity scores were calculated by a logistic regression model, and the PSM analysis was performed using a 1:1 nearest neighbor matching algorithm with a caliper of 0.02 without replacement.18 (DCA), a method for evaluating alternative diagnostic and prognostic strategies, to explore the net benefits between the three scoring systems and intensive care patients with STEMI. The concept of the DCA is generally combining accuracy measures and clinical applicability by integrating clinical consequences associated with a test result. The “net benefit” is calculated by the difference between the proportion of relative harms of false positives and false negatives weighted by the odds of the selected threshold for high-risk designation, therefore the difference between the expected benefit and the expected harm. If it is predicted that the outcome event may occur with a certain probability and the emergency intervention measures  are immediately carried out at the same time, the use of the scoring system corresponding to the largest area under the decision curve will have the greatest clinical benefit.We also performed the decision curve analysis19. DCA was performed by the "rmda" package of R software. P value < 0.05 was considered statistically significant.All analyses were conducted with SPSS software , MedCalc statistical software , and R software . The Z test was performed using MedCalc statistical software by the method of Delong et al.P < 0.001). Age, the level of white blood cell, anion gap, blood urea nitrogen, creatinine, INR, heart rate, and respiratory rate, SAPS II score, LODS score, and OASIS score in the death group was significantly higher than in the survival group , while the level of red blood cell, platelets, hemoglobin, systolic/diastolic/mean blood pressure, and temperature in the survival group was significantly higher than in the death group . There were no significant differences in length of ICU stay and the level of saturation of peripheral oxygen between the two groups. The prevalence of peripheral vascular disease, diabetes, and renal disease was significantly higher in the death group , while the prevalence of hypertension and the proportion of patients who underwent PCI/CABG were significantly higher in the survival group . The baseline characteristics of the study population are presented in Table P > 0.05 for all, see Ppsm in Table 76,540 ICU admissions were contained in MIMIC-IV database, and finally, 522 patients were enrolled in this study  before adjustment. After adjustment, gender, heart rate, and underwent PCI/CABG or not were all independent risk factors for in-hospital mortality; In addition, LODS score and SAPS II were independent risk factors  for in-hospital mortality, while OASIS was not correlated with the mortality   were all risk factors for in-hospital mortality in intensive care patients with STEMI (P = 0.018), LODS vs SAPS II , and OASIS vs SAPS II . The cut-off value corresponding to Youden’s index was selected as the optimal cut-off value for predicting in-hospital mortality. SAPS II had the highest sensitivity (89.42%) and Youden’s index (0.6382), while LODS had the highest specificity (87.80%). The results are presented in Table P = 0.013), LODS vs SAPS II , and OASIS vs SAPS II . LODS had the highest sensitivity (73.40%) and Youden’s index (0.6064), while SAPS II had the highest specificity (90.43%). The results are presented in Table Before PSM, the AUCs of LODS, OASIS, SAPS II were 0.867, 0.827, and 0.894 for the study cohort, respectively , LODS vs SAPS II , and OASIS vs SAPS II . LODS had the highest sensitivity (82.93%) and Youden’s index (0.6024), while OASIS had the highest specificity (83.39%). In the non-PCI/CABG group, the AUCs of LODS, OASIS, SAPS II were 0.857, 0.804, and 0.897, respectively , LODS vs SAPS II , and OASIS vs SAPS II . SAPS II had the highest sensitivity (95.24%) and Youden’s index (0.6190), while LODS had the highest specificity (92.38%). The results are presented in Tables We conducted a stratified analysis of the patients who underwent PCI/CABG or not. In the PCI/CABG group, the AUCs of LODS, OASIS, SAPS II were 0.853, 0.825, and 0.867, respectively  for in-hospital mortality of intensive care STEMI patients for the first time. We confirmed that both LODS and SAPS II have good predictive value, and all AUCs were greater than 0.85. Retrospective studies may have potential biases, therefore we performed a PSM analysis and the results still suggested that LODS and SAPS II have excellent predictive value. Considering whether underwent PCI/CABG or not may have a great impact on the prognosis of the study cohort, we conducted a stratified analysis, and the results still supported the above conclusions. Comparing LODS and SAPS II, there was no significant statistical difference between the two scoring systems , and in most cases, both were higher than OASIS in predictive value.Patients with STEMI remain at increased risk of mortality if they survive the initial ischaemic event9, which is the least among the three scoring systems , which characterizes the severity of the disease. Acute myocardial infarction is the most common cause of cardiogenic shock, and cardiogenic shock can lead to end-organ hypoperfusion (such as the kidney) and tissue hypoxia23. As a result, urine output and PaO2/FiO2 can reflect the severity and prognosis of myocardial infarction (including STEMI) to a certain extent correspondingly. The LODS scoring system has 4 fewer variables than SAPS II, but its predictive value is still comparable to SAPS II, which may be largely contributed by platelets and prothrombin time. Platelet activation and thrombin generation play key roles in intracoronary thrombus formation24. Platelets and prothrombin time largely reflect the conditions of platelet activation and thrombin generation, thus LODS is suitable for predicting the prognosis of STEMI. Although SAPS II contains many variables, electrolyte variables such as potassium, sodium, and bicarbonate tend to reflect the degree of metabolic acidosis in the form of anion gap . For "comorbidity", this variable not only increases the workload when calculating scores but also may be more suitable for the prediction of long-term mortality; in addition, patients with STEMI are often admitted to the emergency department, therefore the variable "admission type" may not be sensitive and specific. In summary, LODS and SAPS II have similar predictive values, but LODS is more concise and maybe more acceptable to clinicians for application.The sophisticated scoring systems require the collection of numerous physiologic measurements, making their applications in clinical practice difficult. The LODS scoring system contains 11 variables, and SAPS II contains 15 variables  risk score and found that TIMI score was acceptably useful (the AUC for the ROC curve was 0.7)27. It should be noted that the above two scoring systems are commonly used to predict medium and long-term mortality, such as 30-day mortality, 180-day mortality, and 1-year mortality. In terms of short-term  predictive value, however, there is still a lack of multi-center large sample clinical evidence. Moreover, GRACE and TIMI score are more difficult to score and require repeated evaluations, which rely heavily on dynamic electrocardiogram (ECG) changes and myocardial injury markers. The three scoring systems in this study are all applicable to ICU, and the predictive value of LODS has been confirmed. Therefore, the LODS scoring system may be more valuable for the prediction of in-hospital mortality for intensive care patients with STEMI.Prior to this, researchers have made some explorations on the prediction of in-hospital mortality of STEMI patients. Koonsiripaiboon et al. used the Global Registry of Acute Coronary Events (GRACE) risk score to predict in-hospital mortality for 209 STEMI patients and found that the scoring system was validated28; last but not least, the clinical strategies for patients with STEMI have changed over this relatively long time period (from 2008 to 2019), for example, from early revascularization of all vessels to revascularization of the culprit vessel only, indication for CABG etc. However, we cannot evaluate the biases caused by the changes. Since this study is a single-center study based on the American population, the conclusions of this study still need to be confirmed by well-designed prospective, multi-center clinical trials.There are several limitations to this study. Firstly, since it is currently impossible to extract imaging data such as ECG and coronary angiography from the MIMIC-IV database, it is difficult to obtain an accurate GRACE score and TIMI risk score. This study did not include the above two scoring systems for comparison; secondly, the database has too many missing values for some myocardial injury markers such as troponin on the first day of admission. We did not take these factors into consideration, which may affect the results; thirdly, the results of before/after PSM and stratified analysis found that the optimal cut-off values of each group were slightly different, which may be related to the variation between groups. Both patient characteristics and center characteristics may affect the results, and may even cause the scoring system to overestimate the mortality rateAmong the three scoring systems, LODS and SAPS II have excellent predictive value, and in most cases, both were higher than OASIS. With a more concise composition and greater clinical benefit, LODS may be a better predictor of in-hospital mortality for intensive care patients with STEMI.


Emerging evidence pointed to a potential association between periodontitis (PE) and rheumatoid arthritis (RA), based on shared characteristics and similarities in risk factors, immunogenetics and pathways of tissue destruction. The aim of this study was to evaluate the potential association between RA and PE, as well as the influence of risk variables in this association.The present case-control study comprised 471 individuals (157 cases with RA and 314 controls) that underwent a full-mouth periodontal examination. The association between risk variables and the occurrence of AR and PE were evaluated through univariate and multivariate logistic analysis. p<0.001), severity (p=0.006) and extension (p=0.018) of PE was observed among the cases when compared to controls. Variables retained in the final multivariate models for the occurrence of PE were: lower number of teeth, smoking, no use of dental floss, ≥4 daily toothbrushing and RA; for the occurrence of RA were: higher age, female gender, smoking, alcohol use and PE. It is important to stress that RA  was retained in the model for PE, and PE  was retained in the model for RA. Higher frequency (The present study demonstrated a high frequency of PE among individuals with RA and an important association among the occurrence, severity and extension of PE and RA and smoking. Key words:Case-control study, risk factors, periodontitis, rheumatoid arthritis. Periodontitis (PE) is characterized by a microbiologically associated inflammation . Its patSeveral studies have demonstrated evidence of the association between PE and several systemic conditions, including diabetes, obesity, cardiovascular diseases, pregnancy disorders and rheumatoid arthritis (RA) ,4. The uRA is a chronic autoimmune disease that causes a breakdown of self-tolerance, chronic inflammation and debilitating joint destruction , compromSome studies -17 pointPorphyromonas gingivalis and inflammatory cells. Thus, P. gingivalis can play a crucial role in breaking immunological tolerance by inducing the citrullination of host proteins, converting them into autoantigens , thus 471 individuals were examined and determined to be eligible for the study. Final sample comprised 157 individuals with RA (cases) and 314 without RA (controls). Control group was composed by appointment companions, relatives, and staff members from the study hospital unit, all of them without RA. Sampling strategy is shown in Figure The present study was approved by the Research Ethics Committee from the Federal University of Minas Gerais, Belo Horizonte – Brazil (CAAE#48355915300005149). All individuals provided written informed consent before enrolling in the study.-Data collectionInterviews were performed through a structured questionnaire, recording the following data: gender, age, general health status, alcohol consumption (frequency / amount), smoking and oral hygiene habits. It was also collected from the medical records of all case individuals data on RA activity through the Disease Activity Score (DAS-28) . The mosIn relation to smoking, individuals were determined to be smokers if they had smoked ≥100 cigarettes throughout life and were still smoking during the study examination period; those who had smoked <100 cigarettes throughout life and were not smoking at the study examination period were determined to be non-smokers .-Periodontal clinical examinationPeriodontal clinical examination was performed with a manual periodontal probe. The following periodontal parameters were evaluated and recorded from all present teeth, except from third molars, at 4 sites : (i) probing depth (PD); (ii) clinical attachment level (CAL); (iii) bleeding on probing (BOP) (iii).-Intra and inter-examiner agreementPeriodontal examinations were performed in 12 individuals by 2 trained and expert periodontists (M.F.M and F.O.C). Intra and inner-examiner agreement for PD and CAL parameters revealed kappa values higher than 0.88 and intraclass correlation coefficient higher than 0.90.-Periodontitis definition and staginget al.  and without tooth loss due to periodontitis. Total periodontitis were defined as the sum of stages II, III and IV, according to the criteria by Tonetti -Rheumatoid arthritis diagnosis Diagnosis and severity of RA  were determined by the rheumatologic medical team of the study hospital, according to the criteria stablished by the American College of Rheumatology . These i-Statistical analysisGroups were initially compared in relation to the following variables: gender, age, smoking (non-smokers / former-smokers and smokers), alcohol consumption, oral hygiene habits, DAS-28 scores and use of medications by the Chi-square and Mann-Whitney tests and Spearman correlation, when appropriate. Regarding the periodontal parameters , the values per individual were obtained by the sum of the measures of all periodontal sites and expressed as means and / or percentages.p-value <0.25 in the bivariate analysis were then included in each multivariate model (non-cases (0) and cases  and their 95% confidence intervals (CI) were calculated. The effect of variables of interest on the occurrence of PE and RA was assessed using the multivariate logistic regression. The Generalized Estimation Equations method was used to obtain marginal logistic models that directly incorporate the correlation between the measures of the same sample unit. Variables with a nd cases ) and remp<0.001). Moreover, individuals with RA showed significantly higher mean age (p<0.001), smokers (p<0.001) and less use of dental flossing (<0.025) and less alcohol consumption (p<0.001). Brushing frequency did not show significant differences between the groups . Individuals with RA presented a 2.64 higher chance of having PE . In addition, the severity (p = 0.006) and extension (p = 0.018) of PE were higher among RA individuals  was observed among cases (53.8%) when compared to controls (30.1%)  remained in the model for AR and AR  remained in the model for PE.p>0.05; data not shown).RA activity by stages  was assessed through the DAS-28 method and correlated with PE. However, there was no significant correlation between DAS-28 scores and periodontal clinical parameters of PD, CAL and BOP, occurrence of PE, as well as in relation to the severity of PE .The use of different medications such as methotrexate, vitamin D, calcium, folic acid, leflunomide and prednisone by individuals with RA did not shown significant differences in relation to the occurrence or the severity of PE (p<0.001). In addition, greater severity and extension of PE were also observed. This association remained in the multivariate models for both PE and RA.The present study showed a higher occurrence of PE in individuals with RA when compared to controls  and citrullinated proteins have been identified in inflamed periodontal tissues, reinforcing the hypothesis that periodontal citrullination may play an important role in the etiopathogenesis of RA , as well as endocrine and behavioral disorders, that can predispose to greater susceptibility to both diseases ,19.Tooth loss is considered the final outcome of oral diseases that affect periodontal and dental tissues, affecting the oral health-related quality of life. In this present study, individuals with RA presented significantly lower number of teeth than controls. Similar results have been previously reported ,28,29.et al.  remained in the model for AR and AR  remained in the model for PE. This reinforces the association between these 2 conditions. In addition, the presence of smoking in both models also reinforces the hypothesis that common risk and susceptibility factors are shared between them.It is important to highlight that in both multivariate models, PE  the high number of individuals in the sample, increasing the statistical power of the study; (ii) the diagnosis of RA by specialized doctors; (iii) the full-mouth periodontal examination with a robust periodontitis definition, since it is recognized that the quality of the periodontal data and the criteria for PE definition can strongly impact the results of the association studies .Future studies with different samples and prospective designs, including microbiological and immunological analyzes, would be of paramount importance to provide more accurate conclusions about the periodontal status of individuals with RA and the association between PE and RA.The present study reported a higher occurrence, severity and extension of PE in individuals with RA. A strong association between RA and PE was observed after adjusting for important confounding variables in multivariate models, including smoking as a common risk factor shared between both conditions.


Depressive symptoms are associated with a decline of episodic memory, but the relationship with semantic memory remains unclear. The aim of the study was to analyze the relationship of depressive symptoms with the semantic memory in a community-based sample of elderly adults. The sample comprised two groups, namely, clinical (with depressive symptoms) and control. The following instruments were used General Evaluation Questionnaire, Montreal Cognitive Assessment-Basic, Wechsler Abbreviate Scale of Intelligence, Geriatric Depression Scale-30 (GDS-30), Beck Depression Inventory-II, Boston Nomination Test (BNT), vocabulary, verbal fluency test , and Brief Cognitive Screening Battery. The results showed a significant difference between groups only in BNT. A significant correlation was observed between the BNT and GDS-30. Participants with symptoms of severe depression performed poorly on BNT when compared with individuals with mild symptoms. These results support the hypothesis that depressive symptoms in elderly adults can affect semantic memory and may worsen with the severity of symptoms. It has a high incidence in the elderly people and can be considered a risk factor for the development of dementia.,,Depressive symptoms can affect cognition in elderly adults. According to Naismith et al.,In another study, Callahan et al.,,,,The relationship between depression symptoms and semantic memory remains unclear.The recruitment was carried out in a community-based sample of 88 adults. The inclusion criteria were as follows: elderly adults above 60 years of age, both sexes, and literate. The exclusion criteria were as follows: patients possibly diagnosed with dementia and having intelligence quotient (IQ) below 70. A total of 13 participants were excluded: 11 with a probable diagnosis of dementia and 2 with IQ below 70. Then, the volunteers were divided into two groups according to the cutoff point established in the performance on two depression scales: Geriatric Depression Scale-30 (GDS-30)The following instruments were used to evaluate participants, divided according to the function evaluated.General Evaluation Questionnaire: This instrument was designed specifically for this research to obtain general information about the participant, including demographic data, previous diagnoses, family history, awareness of general health, and medication use.Montreal Cognitive Assessment-Basic (MoCA-B): Originally developed by Nasreddine,,Wechsler Abbreviated Scale of Intelligence (WASI): It was developed by WechslerGDS-30: Originally developed by Yesavage et al.,BDI-II: It is an inventory created by Beck et al.,Boston Naming Test (BNT): Originally developed by Kaplan et al.,,,Verbal fluency test — animals: it is used to evaluate executive functions and semantic memory. It works by questioning the subject to articulate as many animals as he/she can remember within a minute.Verbal fluency test — fruit: this is one of the MoCA-B subtests used to evaluate executive functions and semantic memory,Brief Cognitive Screening Battery (BCSB): this instrument developed by Nitrini et al.All instruments were applied in a single session, lasting around 90 min. The order of application of the instruments were General Evaluation Questionnaire, MoCA-B, WASI, GDS-30, BDI-II, BNT, verbal fluency test — animals, verbal fluency test — fruits, and BCSB.via the UFPR Press Office and evaluated at the Center for Applied Psychology of the university. All participants signed an informed consent form, which had all questions about the research and guaranteed anonymity.The research was submitted to the Ethics Committee of the Health Sciences Sector of the Universidade Federal do Paraná (UFPR) and approved by number CAAE: 69654817.6.0000.0102. Through the wide dissemination of research in the media, the volunteers were recruited t-test was used. According to the severity of depressive symptoms, the clinical group was subdivided into mild depressive symptoms and severe depressive symptoms. Analysis of variance (ANOVA) was used to compare the symptoms and the severity of the control group. The significance level for rejecting the null hypothesis was p<0.05. To verify the degree of association between the variables, the Pearson correlation coefficient was used. Multiple linear regression (Enter method) was performed to verify the predictive capacity of variables on performance in instruments that assess the semantic memory construct. Finally, to understand the clinical applications of the results, the effect size, Cohen’s d, and η² were calculated. According to Cohen,t-test, we considered 0.20 , 0.50 (medium), and 0.80 (large). For ANOVA, we considered 0.10 , 0.25 (medium), and 0.40 (large).All statistical analyses were performed using the Jamovi software version 0.8.2.3.d variable shows the average effect size in MoCA-B and BNT and small size in vocabulary and verbal fluency test — fruits.Significant differences were observed in the performances of the clinical and the control groups only in BNT . Howevern=24) and severe depression (n=9) and was compared with the control group. The ANOVA showed significant differences in BNT between the three groups. Post-hoc analysis (Bonferroni test) showed that the difference was significant between the control group and the severe depression group (p=0.04) but not between the mild depression and severe depression groups (p=0.427). The control group and the mild depression group showed no significant difference (p=0.538). The analysis also showed the average effect size in BNT.In r=-0.30; p<0.01).The correlations between the tests that evaluate semantic memory and the depression scales are shown in R-squared=0.61 and adjusted R-squared=0.37.This objective of the study was to analyze the relationship between depressive symptoms and semantic memory in a community-based sample of elderly adults. The results showed a significant difference between the clinical (with depression symptoms) and control groups only in BNT. A significant negative correlation was found between GDS-30 and BNT, indicating that the higher the score on the scale, the lower the BNT score. These results support the initial hypothesis that the severity of depressive symptoms affects the impairment of semantic memory.,,,The results in the present study corroborate some studies in the literature.An explanation for this discrepancy is related to the characteristics, particularly demographic characteristics, of the clinical samples. Sheline et al.distributed-only suggests that it would organize according to the neuroanatomy of related systems; (2) distributed plus-hub view defines that there would be a central activation axis formed by a group of amodal neurons that would coordinate the connections and cross information;hub-and-spoke, which proposed the existence of a radial rather than a distributed model, that is, the amodal center (hub) would be located in the anterior temporal lobe and interact with the rays (spokes) that would be specific regions for the modality.However, how can depressive symptoms affect semantic memory? Semantic memory is a neural network of connections distributed across the sensory, motor, and linguistic areas.In other words, the naming task requires the subject to observe the image, activate the sensory, motor, and linguistic areas related to this object, cross the information and correctly identify it, and demand the semantic neural network. Depression implies inhibition of the nervous system; it theorized that semantic connections are also affected by this state, making it more difficult for these patients to access the correct name of the object or, in some cases, increasing the response latency. Neuroimaging studies have found functional abnormalities that affect regulation neurocircuits in patients with depression, involving changes in connectivity between the cortical regions such as the prefrontal cortex (PFC) and subcortical regions amygdala and hippocampus.,Cognitive factors, such as recall, semantic representation, and executive functions, in the structure and processing of semantic memory during the aging process are still a topic of debate.This study had some limitations. It is important to note that there are many variables to be considered in a patient with depression, for example, when depression was diagnosed, medication, and the effect of nonpharmacological treatments. In this study, these variables were not controlled. A cohort study would allow a more detailed understanding of the effects of depressive symptoms on semantic memory.In summary, this study analyzed the relationship between depressive symptoms and semantic memory. The results showed that deficits in semantic memory increase in proportion to the severity of depressive symptoms. The implications of this study suggest that in cognitive assessments and the presence of depressive symptoms in the elderly people, possible deficits in semantic memory should be considered.