There were no differences in recipient demographics and donor details between groups. CIT was significantly longer in the HMP group . The incidence of DGF as well as serum creatinine at discharge and at 1 year post transplant were comparable between groups. Duration of SCS prior to HMP was comparable among grafts with and without DGF. Flow rate and organ resistance at the start of HMP were significantly worse in DGF-kidney grafts . Recipients with DGF had significantly worse creatinine levels at discharge  and at 1 year post transplant . In conclusion, baseline HMP parameters could be applied as a predictive tool for initial graft function, which in turn determines long-term outcome.Kidney allografts are subjected to ischemia reperfusion injury during the process of transplantation. Hypothermic machine perfusion (HMP) of deceased donor kidneys from organ procurement until transplantation is associated with a superior outcome when compared to static cold storage (SCS). Nevertheless, cold ischemia time (CIT) remains an independent risk factor for delayed graft function (DGF) in HMP-preserved kidney allografts as well. We performed a retrospective single-center study including all adult recipients who underwent deceased donor kidney-only transplantation at our center between January 2019 and December 2020. Beside the clinicopathological donor and recipient data, flow and resistance data during HMP were assessed. Short- and long-term kidney allograft outcome after end-ischemic HMP and SCS were analyzed and compared. Organ preservation consisted of either SCS ( Differences between categorical variables were tested using Fisher’s exact test or chi-square test as appropriate. Differences in continuous variables were tested using Student’s t-test or Mann–Whitney test as appropriate. The reference point for all calculations of survival was the day of kidney transplantation. Overall graft survival was determined until patient death, return to dialysis or the end of the study period. A n = 13), recipients of combined-organ transplants (n = 15) and recipients of living donation (n = 39) were excluded from this study. Between January 2019 and December 2020, 200 patients underwent kidney transplantation at our transplant center. Children under the age of 18 ; HMP was applied in 45 (33.8%) donor kidneys. Recipient and donor characteristics did not differ significantly with regards to preservation method, besides dialysis vintage being significantly longer in the HMP group (p = 0.03). CIT was significantly longer in the HMP group with the majority lasting more than 15 hrs; in the majority of the SCS group, CIT was less than 15 hrs (p = 0.0055)Recipients’ demographics are given in n 15 hrs . SCS prin = 57, 42.9%), but comparable between groups . Twelve patients received only one dialysis treatment within the first seven postoperative days, nine of these patients on POD 0 or 1 .Incidence of DGF was high in our entire study population (p = 0.3132).Initial creatinine and creatinine at 1 year post transplant were comparable between both groups . In the Patient survival was 96.2% in our study population and study period. In the SCS group, two patients died on POD 21 and POD 32 due to multiorgan failure, one patient died of unknown causes on POD 355, and one patient died due to SARS-CoV-2 pneumonia on POD 592 with a functioning graft. In the HMP group, one patient died due to pneumonia on POD 16 with a functioning graft.p = 0.7717). Cardiovascular risk factors of donors, such as hypertension  and diabetes , were comparable between groups. Male donor sex was significantly more frequent in recipients with DGF, and there was a trend for a higher recipient BMI in recipients receiving DGF grafts  and at 1 year post transplant . Graft loss was comparable among recipients with and without DGF . Subgroup analysis of DGF grafts vs. immediately functioning grafts in the SCS group and in the HMP group, respectively, did not yield differences in donor and recipient characteristics in these subgroups (Patients with DGF demonstrated significantly higher creatinine levels at discharge (2.54 [1.08–7.64] vs. 1.67 [0.90–6.56], ubgroups .Kidney allografts with immediate function exhibited significantly higher arterial flow and significantly lower organ resistance at HMP start. Both grafts with and without DGF demonstrated a significant increase in arterial flow and a significant decrease in organ resistance already after one hour of HMP. For the further course, arterial flow and organ resistance were comparable between groups . The impSCS is still widely in use for organ preservation due to its simple and cost-effective applicability despite evidence for improved graft function of HMP-preserved kidney allografts . FrequenFurthermore, the extent of the beneficial effects of HMP may depend on the applied definition of DGF, and the thresholds for the use of dialysis may vary between centers. Mallon et al. suggested that the most widely used and most easily calculated definition, i.e., the need for dialysis within the first seven postoperative days, should be universally adopted as the definition of DGF clinically, and as a study endpoint . The effIn our small study cohort, the acknowledged advantage of HMP for the reduction of DGF  did not HMP initiated directly after procurement was proven to result in a significantly improved 1 year graft survival in kidney transplantation compared to SCS . AgainstA Cochrane review identified that current studies fail to provide evidence of a benefit of HMP in terms of graft non-function, and research investigating the use of perfusion parameters to perform viability assessment may be useful in preventing graft non-function . Adani eIn our study, improvement of arterial flow and organ resistance was present already after one hour of HMP in kidney allografts with and without DGF alike; only baseline values demonstrated an increased resistance and reduced flow in DGF kidneys. This is in accordance with results published by Patel et al. achieving average flow rates in the first two hours after perfusion . DespiteKnowledge about the exact mechanism of kidney transplant outcome improvement after pulsatile HMP is still limited. Pulsatile flow is known to prevent vasospasm and to promote vasodilation upon reperfusion; improved microperfusion at the time of reperfusion increases the chances of immediate graft function . NeverthThe present study has some limitations inherent in any retrospective study design with a limited number of patients. Due to the typical application of HMP only at the recipient center, a subgroup analysis of HMP during transport versus HMP at the recipient center alone was not completed. We applied the most widely used definition of DGF, resulting in a high incidence in the entire study population. Protective factors independently associated with an improved outcome were not detected in this small sample size.In conclusion, end-ischemic HMP outweighs the effects of significantly prolonged CIT. Furthermore, baseline HMP parameters could render a predictive tool for initial graft function. Differences in short- and long-term outcomes of kidney transplantation in the setting of prolonged CIT might be more evident in preservation-HMP, and studies analyzing HMP during transport versus at the recipient center alone are still warranted.


With the deepening of the concept of a “global village,” the exchanges between countries in the world are deepening. This has led to ever-closer ties between countries and regions. They are more and more interdependent and mutually restrictive. Internationalization has become an inevitable trend and trend in the development of higher education in the process of globalization. Big data refer to a collection of data whose content cannot be captured, managed, and processed by conventional software tools within a certain period of time, and need to be processed to obtain the required information. Developed countries have developed earlier in the field of education internationalization and have more mature experience, which provides a reference for the development of other countries. This paper aims to study the optimization design of the international talent training model based on the big data system. In this paper, the system analysis method is used for theoretical discussion. It establishes an index system of graduate students’ international talent training mode through AHP, and puts forward a breakthrough for international education in colleges and universities. Internationalized talents refer to high-level talents who have an international awareness and mind, a world-class knowledge structure, a vision and ability reaching an international level, and who are good at seizing opportunities and striving for initiative in global competition. This paper deeply studies the current situation of the international talent training model in colleges and universities, and finds out the deficiencies in the international talent training model. It also optimizes the path for the cultivation and development of international talents, which provides a basis for regional development and cultivation of international talents. The experimental results of this paper show that 20.1% of students believe that international education is to adapt to educational development, 25.4% of students believe that it is mainly to meet the needs of student development, and 62.2% of students believe that college majors lack internationalization characteristics. Talent is the core element of modern country construction, it provides intellectual support for the country’s development. With the advent of globalization and economic integration, the competition between countries has gradually developed into a contest between senior professional international talents with international vision and international knowledge background. College students are the reserve army of talents, so it is imperative to carry out international education for college students. The cultivation of international talents needs to involve big data technology. The big data model research on the quality evaluation of talent training in colleges and universities is mainly reflected in the evaluation, which can show the level of talents as a whole. China has a relatively short development time in international education personnel training, so it needs to learn from the advanced experience of other countries . This paIn order to improve the comprehensive quality of students and cultivate versatile talents with practical ability, education needs to combine big data technology and innovative training models. On the basis of the research on Russian talent training and the use of big data technology, Huang Y proposed a multidisciplinary talent training model featuring culture, language, and interaction. Through the application of the CLI model, optimizing the curriculum system and teaching methods, and building a good learning environment, traditional talent training has been greatly improved . Big datThe concept of big data is now approached from a different perspective, covering its impact in many fields, including healthcare. For a wealth of health information, Bikash began by providing the lay reader with a broad overview of the effectiveness of big data and big data in healthcare. He then built a distributed framework for an organized healthcare model to protect patient data . Money WHuman resources are an important force for national development. With the deepening of internationalization, international talents are an important force for national development. The cultivation of large numbers of people is inseparable from education, so the cultivation of international talents needs the support of international education. Research shows that 43.1% of students believe that the mastery of international professional knowledge is insufficient. 75.6% of the students believe that the foreign language level needs to be improved. 52% of students believe that intercultural communication skills are insufficient. 35% of students believe that personal physical and mental quality is an important aspect that affects the cultivation of international education.As the form of world multi-polarization intensifies, the trend of multi-polarization in both political and economic fields is accelerating worldwide . From thInternationalized talents are strategic resources for countries to improve their comprehensive national strength and competitiveness. Therefore, it is more important to cultivate local talents instead of relying only on foreign talents. According to China’s education system, colleges and universities are important places for cultivating international talents . InternaThe term “cultivation model” was first used in the field of education, but there is no academic explanation for it in the relevant literature, so everyone has different opinions on the meaning. However, it is generally agreed that talent training is a systematic and dynamic process . Figure Strictly speaking, talent cultivation and talent cultivation mode are different concepts. Patterns are an important method of operation. In layman’s terms, it is a bridge. It closely links theory and practice, and uses theory to guide practice. The talent training model can be regarded as a method of teaching activities, but it does not grasp the essence of talent training . The talWith the advancement of science and technology, we need more and more information. With the promotion of the Internet, there are more and more data and information around us, which brings difficulties to the use of information. In order to use the information reasonably, we need to classify various types of data information .Clustering refers to the process of classifying mined data. It can integrate information, analyze data centrally, and maximize the value of data. In the above equation, The division algorithm divides the objects in the data set into several parts, and through repeated iterative calculations, the objective function is continuously reduced until convergence. It is mainly used in the division problems involving some numbers that are difficult to be directly obtained by the combination equation. For example, it divides n numbers into multiple division methods that are not greater than m, and there is no same number, or the problem of dividing them into several odd or even numbers.In The queue intelligent algorithm is a relatively new intelligent algorithm. Because the algorithm is relatively new and has never been widely used in various fields, it is also widely used in the processing of clustering problems. Its algorithm flow is shown in In this cluster analysis, it is not carried out in every generation of evolution, and there are several intervals between them. This method conforms to the operation law of the algorithm, which is beneficial for the algorithm to use the information accumulated iteratively, and conforms to the overall process and trend of intelligent algorithm optimization.In In When all the data are sorted, we can derive the distance represented by each candidate solution. When we combine them together, it can be expressed by the In the above equation, When the data are clustered and analyzed, certain results will be obtained, but the results are not necessarily the best values, so we need to evaluate and analyze them.In G.In actual processing situations, the amount of data is very large. In order to reduce the influence of the data volume on the clustering effect, we need to normalize the data. The above equation translates the data. However, the data are still not standard data at this time, and translation range transformation is still required at this time.In the context of economic globalization, the society’s demand for international talents is getting higher and higher. The internationalization of talents means the internationalization of education. Internationalization of education refers to the integration of local courses with international courses, international exchanges between teachers and students, and technical assistance between cross-border schools. Here, we mainly discuss the internationalization of higher education. Internationalization of higher education is not an end, but a means to cultivate a world-minded, high quality, and ability. From the perspective of historical origin, the internationalization of higher education can be traced back to the reform of the educational system in ancient Greece. Through its continuous exploration and improvement, it enables practice to have theoretical support and improves the quality of teaching and education. The internationalization of early higher education is an individual behavior, which is mainly for the pursuit of knowledge, while the internationalization of modern higher education is more to promote national development and enhance one’s own ability . Figure With the increasing development of economic globalization, the exchanges and cooperation of higher education have gradually increased, and its internationalization trend has become stronger and stronger. It has changed from “government-led” to “college-led.” Its forms and means are increasingly diverse. The competition in the market is becoming more and more intense. Internationalization of higher education is a process from theory to practice. It learns from the experience of other schools with higher education levels and introduces advanced training concepts and goals. At the same time, the internationalization of education development also provides the possibility for the sharing of educational resources.As China’s communication with the world becomes more and more close, it is also more and more in line with international standards in the cultivation of talents. The current talent is an important force for the development of the country, and it is very important to the cultivation of the number of people. From the perspective of the current education system, the most important thing about how to integrate talent training with internationalization is the education method of colleges and universities. For this reason, we conducted a brief survey of the current education system in colleges and universities, as follows.According to the data in Questionnaire surveys can collect data as much as possible, especially electronic questionnaires, which can improve the efficiency of data collection. In order to play its role better, the problem should be designed more rationally and scientifically. In order to investigate the international training situation of colleges and universities, we listed 21 questions. The first 4 of them belong to the basic information of the participants, and we will not introduce them here. Among the questions in the questionnaire, we set 5 questions about the cultivation profile, which reached 23.8%. In addition, we also conducted investigations from the aspects of model evaluation, curriculum design, facility investment, and cooperation and exchanges. It sets up three questions in these four areas, which are 14.3%. From the introduction of the questionnaire, it can be seen that the questions revolve around international talents. It can understand the basic situation of colleges and universities, and at the same time, it can understand students’ views on the system, which provides a basis for our understanding of their training models.When introducing the dimensions of the questionnaire, we pointed out the evaluation settings of the talent training model. This question can reflect the students’ basic attitude towards the school setting. We can analyze the unreasonable aspects of the system and make reasonable adjustments according to the students’ attitudes. The talent training in this university improves the theoretical basis and improves the internationalization level of students. For this reason, we conducted a survey on the evaluation of colleges and universities, as follows.According to the data in As can be seen from the foregoing, in terms of setting up the questionnaire, we have investigated the basic investment in international facilities. For the investment in basic facilities, we mainly discuss the equipment of the laboratory. Based on this, we can see the hardware investment of colleges and universities in talent training.According to the data in International education can drive students to develop in a more comprehensive direction and to integrate with internationalization more quickly. At present, colleges and universities are still in the initial stage in the cultivation of international education, and their understanding of international education is not deep enough. In order to investigate students’ understanding of international education, we conducted a survey and analysis accordingly.International education needs to serve social development. According to the data in Judging from the weakness of college students in international education, 43.1% of the students believed that the mastery of international professional knowledge was insufficient. Professional knowledge is the basic knowledge that talents need to master, and this aspect needs to be strengthened. 75.6% of the students believe that the foreign language level needs to be improved. Foreign language is the basic way of international communication, and it is a communication skill that must be mastered. 52% of students believe that the mastery of intercultural communication is incomplete. Cross-cultural communication is a necessary ability for international talents and needs to be cultivated slowly. 35% of students believe that personal physical and mental quality is an important aspect that affects the cultivation of international education. 57% of students believe that there is a lack of global awareness in international education. According to the above data, foreign language proficiency is the most in need of improvement in international training, followed by a global vision and cross-cultural communication. From this, it can be seen that students basically understand the standards of international talents, and accurately realize which abilities need to be cultivated.In order to explore students’ satisfaction with the cultivation of international talents, we conducted a detailed survey on this dimension. According to the data in Judging from the satisfaction of the talent training process, 65% of the students think that the professional setting is unreasonable, and 58.1% of the students are dissatisfied with the teaching content, 54.8% of the students were dissatisfied with the teaching methods, and 57% of the students were dissatisfied with the teachers in colleges and universities. Most students believe that the course structure and methods are more reasonable and more in line with the needs of students. It can be seen from this that colleges and universities pay more attention to form than practice in international training, and there is still a large distance between the actual teaching link and communicative education.Courses are an important source of knowledge for students, so the design of courses is very important for students. In order to analyze the problems of colleges and universities in curriculum design, we conducted a brief survey of students’ attitudes, as follows.In order to analyze the curriculum design of colleges and universities, we analyze the problems and implementation obstacles of curriculum design. First of all, we need to look at the problems existing in the curriculum design. According to the data in From the perspective of the promotion of internationalized courses, 88 people believed that the unreasonable course setting was caused by the single course structure, accounting for 44%. 114 people think that the curriculum is unreasonable because the curriculum lacks practicality and is difficult to really use. 57% of the students in this group, and 47.5% of the students thought that disdain for the basic courses of international education was the reason why the courses were unreasonable. It can be seen from this that there are few practical courses in international education and training, and it is impossible to transform theory into practice.To cultivate students with internationalization ability, it is not only necessary to design the courses, but also to carry out international exchanges and cooperation in the learning process, so as to cultivate students’ foreign communication ability. At the same time, the international cooperation and exchange activities of colleges and universities are also an important basis for reflecting the internationalization level of colleges and universities. In order to explore the internationalization level of colleges and universities, we conducted a survey on the international exchange activities of colleges and universities. The details are as follows.In order to explore the internationalization capabilities of colleges and universities, we conducted a survey on the local exchange forms and numbers of colleges and universities. According to the data in Judging from the number of international exchanges, basically every project has people participating, which shows that the international cooperation and exchange activities of the colleges and universities are still in progress. However, international school cooperation and exchanges are mainly short-term activities, and these activities have restrictions on the number of students, and many students cannot participate in them, resulting in a low overall level of internationalization. Schools should organize activities that can accommodate multi-person exchanges to meet the developmental needs of students.The wave of economic globalization makes international exchanges more and more closely, and international needs international talents to promote. This requires the country to cultivate international talents. The cultivation of talents is inseparable from education, so colleges and universities have a great responsibility for the cultivation of international talents. The most fundamental thing to establish an internationalized talent training concept is to have a correct understanding and accurate positioning of the value of internationalization. Therefore, this paper aims to study the optimization design of the international talent training model based on the big data system. It expects to use big data technology to provide technical support for the cultivation of international talents and promote the development of education in a more comprehensive direction. In the process of exploration, it is found that the current international education in colleges and universities needs to be improved. Especially in terms of curriculum design and professional setting, it is not at the same frequency as the current development of society. The curriculum lacks practice, and it fails to translate theory. Although this paper has drawn some conclusions, there are still some shortcomings. In the process of using the big data evaluation model to conduct research in this study, although it has been studied, due to personal background constraints, it lacks a broad perspective and the analysis is relatively shallow. It hoped that subsequent studies could explore from a deeper perspective.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.JW: writing—original draft preparation, editing, data curation, and supervision.This work was supported by Key Project of Zhejiang Yuexiu University: Research on Internationalization Strategy of Foreign Language Universities under the Background of New Liberal Arts (Project no: D2020007).The author declares 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 microstructure of legumes plays a crucial role in regulating starch digestion and postprandial glycemic responses. Starch granules are double encapsulated within the outer cell wall and the inner protein matrix of legume cotyledon cells. Despite progress in understanding the role of cell walls in delaying starch digestion, the role of the protein matrix has received little research attention. The aim of this study was to evaluate if the protein matrix and cell wall may present combined physical barriers retarding enzyme hydrolysis of intracellular starch. Intact cotyledon cells were isolated from navy beans and used to assess the barrier effect of the protein matrix on the digestion of starch under conditions simulating the upper gastrointestinal tract. The cells were pretreated with pepsin at 37 °C and pH 2.0 for 1, 4, or 24 h and without pepsin for 24 h (control) to facilitate removal of the intracellular protein matrix prior to cooking and simulated in vitro digestion. A longer pretreatment time resulted in a lower protein content of the cells and a higher initial rate and extent of starch hydrolysis. We suggest that in addition to the primary cell wall barrier, the protein matrix provides a secondary barrier restricting the accessibility of α-amylase to starch. This study provides a new fundamental understanding of the relationship between the structural organization of legume cotyledon cells and starch digestion that could inform the design of novel low glycemic index foods. Epidemiologic evidence supports the association of consumption of nutrient-dense, low glycaemic index legumes with a decreased risk of incident type 2 diabetes and improved glycaemic control in diabetic individuals ,2,3. StaAn accumulating body of in vitro and in vivo evidence has firmly established a link between the microstructure of food legumes and the slow digestion properties of their starch ,10,11,12Recently, there has been a surge of interest in the use of intact, isolated cotyledon cells as a food model to gain a deeper mechanistic understanding of how microscale legume structure controls in vitro starch digestion ,10,11,14To date, most studies have identified the cell wall as a primary physical barrier to starch digestion ,9,13,17.The present study aims to extend our understanding of the role of the protein matrix in determining the kinetics of starch digestion using isolated navy bean cotyledon cells as a food model. Navy beans were selected as the legume variety for investigation due to previous evidence supporting the strong relationship between their cotyledon cell structures and starch digestion in vitro ,11. In tPhaseolus vulgaris L.) was procured from a local store in Palmerston North, New Zealand. Pepsin , pancreatin , invertase (from baker’s yeast (S. cerevisiae), Grade VII, ≥300 units/mg solid), porcine pancreatic α-amylase , soluble potato starch (S-2630), and maltose (S-5885) were purchased from Sigma-Aldrich Ltd., St Louis, MO, USA. Amyloglucosidase  was purchased from Megazyme International Ireland Ltd., Wicklow, Ireland. All other chemicals and reagents were of analytical grade. Reverse osmosis (RO) water was used for all experiments.One batch of raw navy beans  with pepsin. The cell extract (~20 g) collected on the 53 µm sieve  for 5 min each at room temperature and recovered by centrifugation at 1800× g for 20 min. The cells were then spread onto clean glass plates and air-dried in a fume hood overnight at room temperature. The dried powder was bottled and stored at room temperature until further analysis.After the prehydrolysisn step, the cell slurries were transferred to 50 mL centrifuge tubes and centrifuged at 1500× INCs pretreated with pepsin for 1, 4, and 24 h were denoted as INC-1h, INC-4h, and INC-24h, respectively. A control sample (INC-Control) was prepared by treating the cell extract with pepsin-free NaCl buffer  in the shaking incubator at 37 °C and 100 rpm for 24 h followed by ethanol dehydration and air drying. A native sample (INC-Native) was also prepared by subjecting the cell extract directly to the dehydration process without any chemical or enzymatic modification.Moisture content was determined gravimetrically by drying the cell samples in an oven at 105 °C to a constant weight. Crude protein was analysed using the Dumas method (AOAC 968.06)  and a niTotal starch content was quantified using a total starch assay kit (K-TSTA). Total amylose content in starch was analysed using an amylose/amylopectin assay kit (K-AMYL). Both of the starch kits were obtained from Megazyme International Ireland Ltd., Wicklow, Ireland. The analysis was carried out according to the instructions given by the manufacturer. Chemical composition was expressed on a dry weight basis (dwb).w/w) at 90 °C for 30 min according to the method of Leach, McCowen, and Schoch [Swelling power and solubility of starch granules were determined after heating aqueous dispersions of INC, containing approximately 2% starch (d Schoch .w/v) in 20 mM sodium phosphate buffer pH 6.9 in 15 mL Kimax screw-capped glass tubes. The capped tubes were mixed by swirling and placed in a water bath at 20 °C. After 3 min, the reaction was terminated by adding 1 mL of colour reagent solution  to each tube. The tubes were capped, mixed by swirling, and immediately incubated in a boiling water bath for 15 min. After cooling on ice for a few minutes, an additional 9 mL of RO water was added to each tube with inversion to mix the contents. The absorbance of the resulting coloured solution was measured spectrophotometrically at 540 nm. A blank assay was prepared by addition of 1 mL of the enzyme solution after adding the colour reagent and placing the tube in the boiling water bath. A standard calibration curve was prepared from a series of aqueous maltose solutions (0–2.0 mg/mL) and run parallel with the samples. The α-amylase activity was calculated and expressed in units of α-amylase per mg of enzyme powder. One unit (U) of amylase is defined as the amount of enzyme that liberates 1.0 mg of maltose from starch in 3 min at pH 6.9 and 20 °C.Alpha-amylase activities of pancreatin  and α-amylase  were measured using the α-amylase enzymatic assay previously described by Bernfeld . Enzyme The static in vitro digestion protocol described by Dartois, Singh, Kaur, and Singh  was follw/w). The beakers were covered with aluminium foil and placed in a water bath at ~95 °C for 20 min to simulate cooking conditions. Cooked samples (~170 g) were subsequently cooled and introduced into 500 mL jacketed glass reactors. Temperature was maintained at 37 ± 1 °C by circulating water through the reactor jackets. pH was controlled using a pH meter and adjusted by manual addition of HCl (1.0 and 0.5 M) and/or NaOH (1.0 and 0.5 M). The content of each reactor was mechanically agitated using a magnetic stirrer bar at 300 rpm throughout digestion.INCs were suspended in RO water in 400 mL glass beakers to obtain aqueous samples containing approximately 4% starch (w/w) at pH 1.2 for 30 min to simulate gastric digestion. After the gastric phase, the pH was adjusted to 6.8. The reactor contents were then incubated with the SIF containing pancreatin , amyloglucosidase , and invertase  for 120 min to simulate small intestinal digestion.The reactor contents were first incubated with the SGF (17 mL) containing pepsin  were incubated with 0.5 mL of amyloglucosidase and invertase in acetate buffer (0.1 mL amyloglucosidase and 3.75 mg invertase per 10 mL acetate buffer) at pH 5.2 and 37 °C for 10 min to completely convert soluble dextrins in the supernatants to glucose. The glucose released was quantified using a D-glucose assay kit .Duplicate aliquots (0.5 mL) were withdrawn from the reactors after 1, 15, and 30 min of the gastric phase, and after 1, 5, 10, 15, 30, 60, 90, and 120 min of the small intestinal phase. The aliquots were immediately mixed with 2 mL of absolute ethanol in 15 mL centrifuge tubes to stop the enzymatic reaction. The resulting mixtures were vortex-mixed and centrifuged at 1800× SH is the percentage of starch hydrolysis (%), The percentage of starch hydrolysis at each sampling time point was used to construct hydrolysis curves and calculated using Equation (1):The initial rate of starch hydrolysis for the first 10 min of reaction (R10), according to Ezeogu, Duodu, and Taylor , was calAs illustrated in Four experiments (Exps.) were conducted as follows: Exp.1: control with gastric pepsin (GP) in the SGF followed by pancreatin containing pancreatin proteases (PP) in the SIF.Exp.2: only PP in the SIF.Exp.3: only GP in the SGF.Exp.4: without any protease.For Exps. 3 and 4, porcine pancreatic α-amylase (PPA) was used in place of pancreatin  to achieve the unit of α-amylase activity per mL of the final digestion mixture (U/mL) similar to that of pancreatin. The α-amylase activities (U/mg solid) of enzymes were determined using the protocol of Benfield  as detaiw/v) Lugol’s iodine solution and visualised under LM for detecting the presence of starch.For light microscopy (LM), INCs were mounted onto glass microscope slides, suspended in water, sealed with coverslips, and then viewed under an Axiophot light microscope  operating in brightfield mode using the objective of 20× magnification. Representative light micrographs of cells were captured using a Leica DFC320 camera equipped with the Leica software application suite LAS V3.8 . Digesta samples taken after 0 and 120 min of the small intestinal digestion were stained with 2% (For scanning electron microscopy (SEM), INCs were directly mounted on double-sided adhesive tapes on aluminium stubs, sputter coated with gold , and viewed under a scanning electron microscope . Representative electron micrographs of cell samples were captured with accelerating voltage of 25 kV and using the xT microscope software version 3.0.7 .p ≤ 0.05) between means using Minitab 18 software .Data were reported as means ± standard deviations for triplicate determinations unless otherwise specified. Tukey’s test and analysis of variance (ANOVA) were used to assess the significance of differences (Isolated navy bean cotyledon cells (INC) were obtained using the sequential acid-alkali method . This method enabled the easy separation of raw, intact cells without disrupting cell wall integrity and gelatinising starch. Representative light micrographs of INC A–E confiThe microstructure of each native INC A consistNoticeably, the protein matrix appeared dark in contrast to the lighter background when viewed under LM A–D. The As is clearly shown by SEM micrographs in w/w, dwb). These values are within the range of previously published data [The physicochemical properties of the INCs (control and pepsin-treated) and INS are presented in 1. The control INCs contained 64.3% starch and 17.6% protein (hed data . Specifihed data .p ≤ 0.05). These quantitative results support the earlier LM observations of the visual disappearance of the protein matrix in pepsin-treated cells. Additionally, INS contained 91.9% and 0.3% of starch and residual protein, respectively. The amylose content was similar (~28%) across all samples (p > 0.05), indicating that neither the pretreatment duration nor pepsin had any effect on the amylose content.Furthermore, it is evident from p > 0.05). Only prolonged incubation with pepsin up to 24 h could result in significantly higher levels of SP and SS (p ≤ 0.05). It has been suggested that the suppressed swelling and gelatinisation of starch granules entrapped in isolated cotyledon cells of legumes is attributed to limited water availability and spatial constraints inside cells [Moreover, de cells ,28. Thisde cells . TherefoIt is also worth noting that, a vast proportion of the protein matrix (~85%) was effectively removed from the cells by pepsin after 24 h. Despite this, INC-24h exhibited considerably lower SP and SS compared to INS from which the cell structural barriers had been completely removed. This implies that the remaining proteins and the intact cell walls of INC-24h prevented complete starch gelatinisation together. From these findings, it appears likely that the limited SP and SS of INCs are linked to the barrier effects exerted by the cell wall and the protein matrix. These physical barriers combine to inhibit the swelling and gelatinisation of the intracellular starch granules during hydrothermal processing.Cooked samples of the control and pepsin-treated INCs, differing in their protein content, were subjected to in vitro gastric and small intestinal digestion. A cooked INS sample was included as a reference. Starch hydrolysis curves are shown in p ≤ 0.05). The percentage of starch hydrolysed at 120 min of small intestinal digestion  decreased in the following order: INS (85.1) > INC-24h (80.6) > INC-4h (77.6) > INC-1h (73.2) > INC-Control (70.6). In a somewhat similar pattern to that seen in H120, the initial rate of starch hydrolysis  calculated for the first 10 min of reaction when it was highest decreased in the following order: INS (2.76) > INC-24h (2.11) ≈ INC-4h (2.07) > INC-1h (1.50) ≈ INC-Control (1.40). Evidently, both R10 and H120 progressively increased as the duration of the pepsin pretreatment increased from 1 to 24 h. These results demonstrate that the enzymatic removal of the protein matrix improves the rate of amylolysis at the initial stages of in vitro digestion and ultimately enhances the starch digestibility of INCs. This clearly proves that, aside from the intact cell wall, the protein matrix acts as an additional barrier to α-amylolysis of the enclosed starch. Similar findings have been previously reported for kidney bean cotyledon cells by Rovalino-Córdova et al. [As noted in a et al. , althougStaining of INCs with iodine enabled the visualisation of changes in the starch content. The blue–black colour intensity of amylose-iodine complexes is thought to be proportional to the amount of starch present in the cells, thus providing qualitative information on the extent of starch hydrolysis at specific digestion times. Emptying of the cellular contents and a decrease in iodine staining intensity were observed after 120 min in all samples. This effect occurred to a much greater extent in those with a longer duration of pepsin pretreatment. Evidently, in comparison with INCs preincubated with pepsin for only 1 h, those preincubated for 4 h or longer exhibited emptier cellular contents and greater reductions of iodine staining intensity after their exposure to small intestinal conditions, supporting their higher extents of amylolysis (H120) determined quantitatively. These findings are in line with previous reports investigating in vitro starch digestion kinetics of legume cotyledon cells ,18,29.It is also noteworthy that the pretreatment of native INC with pepsin resulted in only partial protein hydrolysis. After 24 h, approximately 85% of protein digestion was achieved as calculated from In an attempt to separate the net contribution towards the barrier effect of the protein matrix from that of the intact cell wall, Rovalino-Córdova et al.  incubateThe starch–protein matrix, consisting of a compact protein matrix entrapping starch granules, is a distinctive microstructural feature of some natural and processed foods. Starch–protein interactions and physiochemical characteristics of the protein matrix  may play a pivotal role in retarding α-amylase digestion of starch, resulting in foods with slow starch digestion properties and potential to modulate glycaemic response ,31,32. HAs demonstrated above, the protein matrix plays a crucial part in limiting in vitro digestion of starch in INCs. Since dietary proteins are susceptible to proteolysis catalysed by GP in the SGF and PP (mainly trypsin and chymotrypsin) in the SIF, it is necessary to further explore the indirect effect of these proteolytic enzymes on starch digestion.The quantitative data clearly show that both R10 and H120 values were significantly reduced when cooked control INCs were digested in the absence of all proteases. This is consistent with previous work conducted by Rovalino-Córdova et al. ,19. ThesOverall, the results of this study have provided strong evidence that the natural presence of proteolytic enzymes in both the stomach and the small intestine of the human GI tract is necessary for efficient in vitro digestion of starch inside INCs. Initially, GP is likely to play a role in loosening the compact starch granule–protein matrix. Subsequently, extensive protein degradation by PP in the small intestine may facilitate enzyme mobility within the cell cytoplasm and enhance starch–amylase interactions. Considering the facilitating effect of proteolytic enzymes on starch digestion, the encapsulation of starch granules in double-layered INC with the protein matrix (inner layer) being surrounded by the cell wall (outer layer) seems to be advantageous in the sense that the protein matrix is shielded from proteases, making it more resistant to proteolysis while providing extra protection for starch.The present study has unveiled intriguing new insights into the role of the protein matrix in modulating the in vitro digestion of starch in navy bean cotyledon cells. We have shown that the entrapment of starch granules in the protein matrix may restrict their swelling and gelatinisation. In addition to the cell wall, the protein matrix presents a secondary physical barrier blocking the access/binding of α-amylase to starch. Proteolytic degradation of the protein matrix removes these restrictions, rendering starch more susceptible to α-amylolysis. Hence, efficient protein hydrolysis before or during simulated GI digestion is a necessary prerequisite for improving starch digestibility. Finally, as proposed by Do, Singh, Oey, and Singh , the uni


Peripheral pulmonary lesions (PPLs) are frequent incidental findings in subjects when performing chest radiographs or chest computed tomography (CT) scans. When a PPL is identified, it is necessary to proceed with a risk stratification based on the patient profile and the characteristics found on chest CT. In order to proceed with a diagnostic procedure, the first-line examination is often a bronchoscopy with tissue sampling. Many guidance technologies have recently been developed to facilitate PPLs sampling. Through bronchoscopy, it is currently possible to ascertain the PPL’s benign or malignant nature, delaying the therapy’s second phase with radical, supportive, or palliative intent. In this review, we describe all the new tools available: from the innovation of bronchoscopic instrumentation  to the advances in navigation technology . In addition, we summarize all the PPLs ablation techniques currently under experimentation. Interventional pulmonology may be a discipline aiming at adopting increasingly innovative and disruptive technologies. Peripheral pulmonary lesions (PPLs) are focal radiographic opacities undetectable by flexible bronchoscopy direct inspection ,2. DetecPPLs may correspond to benign and malignant entities localized at the periphery of the lung. According to the National Lung Screening Trial findings, the early diagnosis of PPLs is associated with a 20% reduction in lung-cancer-specific mortality . Thanks Histological diagnosis is of paramount importance to early detect malignant lesions. The decision whether to proceed to the histological sampling of the PPL depends on the radiographic appearance of the lesion and the presence of various patient’s related risk factors. Hence, when a PPL is identified, it is necessary to proceed with a risk stratification based on the patient profile and the characteristics found on chest CT. Patients with PPL are often asymptomatic, and when symptoms are present, they may reflect the etiologic condition underlying the development of the PPL . Risk faPrimary lung cancer comprises an extensive range of histological types ,20. The Among NSCLC, we should further categorize a few histotypes: squamous cell carcinoma  ,23, adenPatients frequently have an advanced stage of disease at the time of diagnosis due to the delay of symptom presentation, especially for PPLs, which impairs survival . FortunaThe first-line examination is either a bronchoscopy with tissue sampling or computed-tomography-guided transthoracic needle aspiration (CT-TTNA) . TraditiFluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET-CT) may add relevant information in the staging and risk stratification phase of a PPL, especially for solitary pulmonary nodules. It is considerably more likely that solid lung nodules larger than 8 mm in diameter that do not significantly uptake 18F-FDG are benign . HoweverNotwithstanding, over the last years, several novel tools have improved the traditional endoscopic techniques for the diagnostic sampling and, eventually, staging of PPLs. Ultrathin bronchoscopy, radial-probe endobronchial ultrasound (RP-EBUS), virtual navigation bronchoscopy, electromagnetic navigation (EMN), shape-sensing navigation, augmented fluoroscopy, cone-beam computed tomography (CBCT), and robotic bronchoscopy (RB) are now game changers for the interventional pulmonologist (IP). As will be discussed in this review, these minimally invasive procedures aimed at both diagnosis and therapy of PPLs, have been recently introduced in real-life practice, and their safety and efficacy are still under evaluation. We strongly believe that these techniques will lead to a general improvement in the prognosis and personalization of the patient management path.This narrative review evaluates the existing literature by collecting the primary English language bibliographic references in international scientific databases . The search strategy aimed to include the most significant documents dealing with the diagnosis of PPLs by using the following keywords in combination with the Boolean operator OR and: interventional pulmonology, bronchoscopy, lung nodule, peripheral lung lesion, lung cancer, lung cancer screening, endobronchial ultrasound, ultrathin bronchoscopy, lung navigation, robotic bronchoscopy, cone-beam computed tomography, and lung ablation. The interval considered by the research was from January 2009 to November 2022. Other references considered significant were included by the authors.Systematic reviews with meta-analyses, randomized control trials (RCTs), and research were included in our review. We also reviewed the guidelines for diagnosing pulmonary lesions by the leading scientific societies.To minimize bias, two authors  independently carried out the search, deduplicated the research results, screened the articles, and selected the studies to be included in this review. Of note, the list of included references is not necessarily all-encompassing but reflects the body of evidence believed appropriate to the purpose of this document: highlighting the latest progress made in the endoscopic diagnosis and therapy for PPLs.When a PPL is identified, the IP decides whether and how to approach it based on the lesion’s morphology outlined on the chest CT scan ,54. CT pDuring the navigation to the lesion and sampling procedure, the IP will consider all aspects aimed at maximizing the diagnostic yield: adequate sedation of the patient, collection of at least five bioptic samples, and the use of rapid on-site evaluation (ROSE) of the sample on slides set up in the endoscopic room. These considerations maximize the possibility of achieving success in reaching and withdrawing a significant sample from the lesion and minimizing the risk of repetition of the procedure due to insufficient tissue material ,60,61,62The latest guidelines from the American College of Chest Physicians encourage using minimally invasive modalities . NonetheAll the technologies available for the IP may improve the performance of PPL sampling procedures .In the past, flexible bronchoscopy (FB) did not allow direct visualization of the more peripheral airways, as the caliber of the instrumentation available for the adult patient was large. For this reason, since 1985, Prakash hypothesized using small-sized pediatric bronchoscopes to navigate to the periphery and to reach and sample PPLs . HoweverAlthough a universal definition of ultrathin bronchoscopy does not exist, experts generally consider ultrathin bronchoscopes as those with an outer diameter of 2.8–3.5 mm ,65. The Even though the ultrathin bronchoscope can reach the most distal airways, it might not allow direct visualization of PPLs. For this reason, its use may be combined with RP-EBUS, fluoroscopy, and navigation systems to address this limitation. The diagnostic yield for the multimodal sampling of PPLs may exceed 70% and is strictly associated with the lesion’s size and the presence of the bronchus sign ,67,68.Both convex-probe endobronchial ultrasound (CP-EBUS) and RP-EBUS may aid PPLs sampling. CP-EBUS allows direct observation and a contemporary minimally invasive sampling of anatomical structures beyond the airway walls . It can RP-EBUS represents a way to confirm the real-time positioning of the bronchoscope relative to the lesion to be sampled. By locating the area surrounding the PPL, RP-EBUS maximizes the sample quality and reduces the risk of iatrogenic pneumothorax ,72,73. IOverall, the diagnostic yield of bronchoscopy with RP-EBUS for PPLs has been estimated at around 69–73% ,80. As eAccording to the ACCP guidelines, RP-EBUS should be prioritized for the first sampling of PPLs .FB aimed at sampling PPLs has been historically performed under fluoroscopic guidance . HoweverA significant limit of these technologies is the presence of a high discrepancy between the position of the PPL estimated by the navigation technology and its actual anatomical position. The difference between the PPL’s theoretical and actual position has been defined as CT-to-body divergence and represents a phenomenon explained by the dynamic condition of the lung parenchyma during the procedure . The lunThe navigation technologies that have first been introduced in clinical practice are virtual bronchoscopy and electromagnetic navigation (EMN). Virtual bronchoscopy is a CT-based imaging technique that allows a noninvasive intraluminal evaluation of the tracheobronchial tree. In addition, the airways’ and carina’s mucosa morphology may be evaluated noninvasively, and airway exploration via imaging software may aid in the mental mapping of the route to the PPL .Virtual navigation bronchoscopy  uses the patient’s CT scan to represent the airway via pattern recognition software . In otheEMN  initial trials occurred in 2005 . The tecShape-sensing navigation  is a novel guidance system sold only in conjunction with the ION robotic bronchoscopy technology, which tracks the position of a dedicated articulating catheter . A thin Implementing CBCT in clinical practice represented one of the last decade’s most critical advances in interventional pulmonology. This type of technology uses a rotating C-arm that generates intraprocedural images with a quality almost similar to a chest CT ,109,110.Multiple companies have developed their version of both portable and fixed CBCT systems ,117,118.Augmented fluoroscopy (AF) is a novel technology that combines a baseline CT image derived from either a preprocedural chest CT or an intraprocedural scan performed by CBCT with real-time fluoroscopic guidance . This tep = 0.026 for lesions ≤ 10 mm, and 77.5% vs. 46.4%, p = 0.016, respectively, for lesions between 10 and 20 mm).CBCT combined with AF has shown a significantly high diagnostic yield . RecentlRobotic endoscopic systems for bronchoscopy (RB) are experiencing a progressive global diffusion, limited, as for most iconic robotic technologies, by the high cost of acquiring the technology and its consumables ,125.Currently, only two platforms are available , with more to come . Both deOther promising technologies are awaiting final scientific support for their widespread implementation in clinical practice.Confocal laser endomicroscopy (CLE) allows in vivo imaging of tissues. Alveolar spaces may be visualized with a miniprobe (Alveoflex), usually introduced in the lung periphery with a guide sheath . This teOptical coherence tomography (OCT) is an imaging technique based on near-infrared light. The dedicated radial probe creates images using near-infrared light scattering with a 15 µm resolution. OCT provides an advantage over endobronchial ultrasonography because light waves can be used in air-filled anatomical compartments without requiring a transducing medium or direct contact with the tissue . The sysCurrent guidelines recommend surgical resection for early-stage NSCLC in patients eligible for radical treatment . HoweverPotential uses for bronchoscopy include pleural dye marking of PPLs for surgical resection ,154,155,Dye marking of a PPL has a practical utility in identifying lesions otherwise not visible or palpable by the surgeon, allowing shorter operating times and possibly carrying out minor resection operations, such as segmentectomies or wedge resections ,159. IndFiducial markers (FMs) for radiotherapy may be positioned with EMN or RP-EBUS guidance ,156. GenBronchoscopic ablation technologies  include RFA uses an electromagnetic wave, delivering a thermal injury to the PPL via an electrode inserted directly into the lesion . The theMWA employs microwave frequency ranges between 300 MHz and 300 GHz to induce coagulative necrosis by heating the tissue at temperatures above 60 °C. The MWA antenna is usually set at a power level between 40 and 80 W, and the duration of exposure time ranges between 5 and 10 min for each PPL depending on its features .  MultiplePDT requires the preprocedural intravenous administration of a photosensitizing agent (a haematoporphyrin derivative) preferentially taken up by malignant cells . Next foBrachytherapy involves the endoluminal administration of high-dose radiation therapy. This technology was previously applied to central airway malignancies but has been gradually abandoned. Only one study using this technology in the PPL research field has been completed (NCT00107172). Moreover, there are no currently ongoing clinical trials .Cryoablation induces cell death using an alternation of freeze and thaw cycles. Although still not widely used, a Japanese trial has shown good survival following the cryoablation treatment of an inoperable NSCLC ,182. TreLaser ablation or bronchoscopic laser interstitial thermal therapy (BLITT) is an evolution of the classic treatment of centrally located endobronchial lesions ,184. A dBronchial thermal vapor ablation entails the delivery of steam at a high temperature causing colliquative necrosis of the tissues distal to the treated area. Bacterial pneumonia and inflammatory pneumonitis following treatment are frequent . It may Direct therapeutic injection aims at the intralesional administration of therapeutic drugs at high concentrations, limiting systemic administration side effects. The first evidence of the application of this technique dates back to 1980, using various chemotherapy agents. Current clinical trials aim to define whether direct therapeutic injection of immunotherapy or gene therapy mediated by a viral vector can improve quality of life and overall survival .At present, most early human studies perform ablation followed by surgical resection. For individuals who are clinically inoperable, endoscopic ablation may be a therapeutic option with evident benefits over the treatments that are now available. Although many ablative methods have been put forth, most of the data has come from animal research. However, there are several human studies in progress globally. We can only hope that they will overcome the myriad difficulties that this innovative technology faces, so that it can eventually be used in the real-life setting .The field of diagnostic and therapeutic bronchoscopy is ever-expanding. Whenever possible, instead of proceeding with peripheral navigation, it is preferable to resort to shorter and simpler procedures, such as sampling one or more mediastinal adenopathies through endobronchial ultrasound-guided transbronchial needle aspiration. However, when it is essential to reach for a PPL, the development of smaller endoscopic devices and improved navigation systems has led to the ability to reach deep into the lung. We strongly believe that, when used in conjunction, these tools may overcome the diagnostic yield plateau and reach better results. Currently, there is not a single modality or a standardized combination of modalities to be recommended.The desirable goal is an integration of the techniques mentioned above based on the IP expertise, the characteristics of the lesions, and the consideration of patients’ comorbidities. Furthermore, the ultimate goal for every IP should be to provide an adequate diagnosis for a PPL with its staging within a single procedure and, in the future, a radical endoscopic therapy.


Malaysian Journal of Medical Sciences (MJMS) in 2021. It includes the important metrics of journal impact measurement and the appointment of experts within their respective fields as new members of the Editorial Board.This is a report on the annual performance of the  Malaysian Journal of Medical Sciences (MJMS) throughout 2021. Data were extracted from the manuscript submission platform and the calculation data of research metrics by various companies were searched through the Internet.The Editorial Office presents this report on the performance of the In the publication year of 2021, MJMS received a total submission of 766 new manuscripts, which was 7% higher than in the preceding year .Original Article manuscripts comprise the majority of manuscript types submitted to MJMS for the past years, followed by Review Article manuscripts. In particular, the submission of Original Article manuscripts has increased by 30.6% in 2020 compared to submissions in 2019 and showed a slight increase of 6% in 2021. The same submission trend is observed for Review Articles, as shown in The average number of manuscript submissions in 2021 was 64, in which the same highest number of submissions (75 manuscripts) were recorded in April and August, respectively, compared to other months. A comparison of submission patterns of the preceding years is shown in Manuscript contributions to MJMS are exclusively led by researchers from Malaysia. Universiti Sains Malaysia is the local institution that has contributed the highest number of manuscripts to MJMS ever since it started publication. Other local institutions that can be considered major manuscript contributors to MJMS are Universiti Kebangsaan Malaysia and the Ministry of Health Malaysia, followed by foreign institutions, such as the University of Indonesia and Islamic Azad University of Iran, as shown in According to the Academic Accelerator , the 202The H-index is a means of measuring the productivity and citation impact of a publication. According to the SCImago Journal Rank (SJR) , the H-iThe SJR is an indicator that measures a journal’s scientific influence. It considers the number of citations received by a journal and the importance of the journals from which these citations come. According to SJR, MJMS has a ranking 0.433 in 2021 compared to 0.394 in 2020.The impact score of an academic journal, also denoted as the journal impact score (JIS), is a measure of the annual average number of citations in recent articles published in that journal. The impact score of MJMS in 2021 is 1.82. This impact score, which is based on Scopus data, increased by a factor of 0.43. Furthermore, the approximate percentage change is 30.94% compared to the preceding year (i.e. 2020), indicating a rising trend  6)..6).CiteScore is a metric for measuring journal impact in Scopus. It is measured within a 4-year citation window and is calculated from the Scopus journal list, which covers all subject areas. MJMS welcomes Dr. Evelyn Tai Li Min of the School of Medical Sciences, Universiti Sains Malaysia, to the Editorial Board of MJMS. She has been appointed as a subeditor of MJMS, effective 1 May 2021.In early July 2021, we also welcomed other new members to the statistical editor team of MJMS: Ms Fairuz Fadzilah Rahim of the Royal College of Surgeons in Ireland (RCSI) and University College Dublin (UCD) Malaysia Campus, Pulau Pinang, Malaysia; Mr Hazwan Mat Din of Universiti Putra Malaysia, Selangor, Malaysia; and Dr. Nurzulaikha Mahd Ab.lah of the School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.


For more than 40 years, under the leadership of four editors and two publishers, The International Journal of Aging and Human Development (IJAHD) has featured multidisciplinary scholarship related to aging processes and older adults. With the publication of eight issues a year, with over 800 pages of scientific content, the IJAHD places emphasis upon psychological and social studies of aging and the aged. However, the Journal also publishes research that integrates observations from other disciplines that illuminate the "human" side of gerontology. A more recent focus includes midlife development, as well. About half (47%) of the publications in the IJAHD are from international colleagues. This presentation will discuss tips for both international and US-based scholars for ensuring timely reviews and positive decisions for manuscript submissions, including such areas as key words, suggesting unbiased reviewers, formatting, writing mechanics, clearly-articulated methods, and a sound theoretical basis.


Coronary artery bypass grafting remains one of the best therapies foradvanced coronary artery disease. The most used conduit remains the greatsaphenous vein, which is susceptible to short-term and long-term failure,the result of acute thrombosis, intimal hyperplasia, and late superimposedatheroma. In this review, we present the current findings related to thepathophysiology of vein graft failure.A search of three databases - MEDLINE®, Web of Science™, andCochrane Library - was undertaken for the terms “pathophysiology”,“prevention”, and “treatment” plus the term “vein graft failure”.The pathophysiology of saphenous graft failure can be classified in threedistinct phases - acute thrombosis, intimal hyperplasia, and acceleratedatherosclerosis. All these processes start with an underlying histologicalpredisposition of the vein and at the time of harvesting and preparation forgrafting. These mechanisms are a result of localized inflammatory andprothrombotic cascades that obey different causes, but ultimately result inthe stenosis or occlusion of the vein graft.The interaction between the different parts of the pathophysiology of veingraft failure is extremely complex and variable. Recent improvements insurgical techniques and secondary pharmaceutical prevention like earlyaspirin administration and long-term statin treatment have significantlyreduced early and late saphenous vein graft failure. However, this continuesto be a fascinating area of research with the potential for furtherimprovement for patients and health service provision. Activated ECs also produce a particular set ofECM proteins that when detected by the VSMC causes these cells to switch fromthe quiescent and contractile state to the active and proliferativeone29][. Some authors even suggest preoperative veinmapping to select the best conduit47][. Proponents of the technique have shown that theperivascular tissue has an important role in interrupting the pathophysiologydescribed above by increasing the local concentration of NO25][.One of such interventions that has demonstrated to improve the rates of successhas been harvesting the vein with its pedicle and with minimalmanipulation52][. The long-term results inpopulation studies of the efficacy of using this medical therapy will be seen inthe next five to 10 years, but the initial findings are encouraging.For many years, the main drug used to prevent graft failure was aspirinaloneThe pathophysiology of vein graft failure is a complex interaction of severalmechanisms, and this manifests in patients who are already suffering fromatherosclerosis, making the interaction between these processes even more complex.Nonetheless, continuous research in this area over the last decades has provided uswith a more in-depth understanding of the pathophysiology and paved the way tobetter techniques and treatments that decrease the incidence of SV graftfailure.Despite all we have learned on the process of this condition, much still remains tobe learned, and potential therapeutic targets already discovered are still in needof experimental testing. Continuing this line of research may further improve thequality of treatment provided when performing CABG and, therefore, affect morbidityand mortality in the population.


This randomized clinical trial investigates the effect of a combined drug approach targeting the preimplantation liver graft and recipient on the severity of ischemia-reperfusion injury during transplant. Can a combined drug approach targeting the preimplantation liver graft and recipient attenuate the degree of ischemia-reperfusion injury?In this open-label randomized clinical trial of 72 liver transplant recipients allocated to either static cold storage (standard of care) with an add-on combined drug approach delivered to the preimplantation liver and recipient or to standard of care only, peak aspartate aminotransferase serum levels and other functional, laboratory, and survival outcomes were similar between groups.The findings suggest that use of a downstream combined drug approach that targets the preimplantation liver graft and recipient is not clinically effective for decreasing ischemia-reperfusion injury. In a porcine model of liver transplant, a combined drug approach that targeted the donor graft and graft recipient reduced ischemia-reperfusion injury, a major hurdle to the success of liver transplant.To assess the effect of a clinical form of a perioperative combined drug approach delivered immediately before implantation to the procured liver and to the liver recipient on the degree of ischemia-reperfusion injury.This unicentric, investigator-driven, open-label randomized clinical trial with 2 parallel arms was conducted in Belgium from September 2013 through February 2018, with 1-year follow-up. Adults wait-listed for a first solitary full-size liver transplant were screened for eligibility. Exclusion criteria were acute liver failure, kidney failure, contraindication to treatment, participation in another trial, refusal, technical issues, and death while awaiting transplant. Included patients were enrolled and randomized at the time of liver offer. Data were analyzed from May 20, 2019, to May 27, 2020.Participants were randomized to a combined drug approach with standard of care (static cold storage) or standard of care only (control group). In the combined drug approach group, following static cold preservation, donor livers were infused with epoprostenol ; recipients were given oral α-tocopherol and melatonin prior to anesthesia and intravenous antithrombin III, infliximab, apotransferrin, recombinant erythropoietin-β, C1-inhibitor, and glutathione during the anhepatic and reperfusion phase.The primary outcome was the posttransplant peak serum aspartate aminotransferase (AST) level within the first 72 hours. Secondary end points were the frequencies of postreperfusion syndrome, ischemia-reperfusion injury score, early allograft dysfunction, surgical complications, ischemic cholangiopathy, acute kidney injury, acute cellular rejection, and graft and patient survival.P = .49) . There also were no significant differences in the secondary end points between the groups.Of 93 randomized patients, 21 were excluded, resulting in 72 patients (36 per study arm) in the per protocol analysis . Peak AST serum levels were not different in the combined drug approach and control groups (geometric mean, 1262.9 U/L  vs 1451.2 U/L ; geometric mean ratio, 0.87 ; In this randomized clinical trial, the combined drug approach targeting the post–cold storage graft and the recipient did not decrease ischemic-reperfusion injury. The findings suggest that in addition to a downstream strategy that targets the preimplantation liver graft and the graft recipient, a clinically effective combined drug approach may need to include an upstream strategy that targets the donor graft during preservation. Dynamic preservation strategies may provide an appropriate delivery platform.NCT02251041ClinicalTrials.gov Identifier:  Since IRI has multiple pathogenetic pathways, a multitarget pharmacological strategy that interferes with several steps in the IRI cascade is likely to be more effective.21 Preclinical evidence to support this comes from work by some of us in a stringent porcine DCD model of liver transplant and severe IRI in which a combined drug approach (CDA) consisting of agents that target well-known pathogenic IRI mechanisms was used.9 Streptokinase and epoprostenol were flushed through the liver prior to static cold storage, and the recipient received intravenous glycine, α1-acid glycoprotein, mitogen-activated protein kinase inhibitor, α-tocopherol, and glutathione.10 The CDA allowed for a steady and spontaneous liver function recovery, eliminated primary nonfunction, and improved recipient survival; it prevented Kupffer cell activation and subsequent tumor necrosis factor α production, stabilized glutathione depletion, and reduced redox-active iron and bile salt toxicity.10 In a subsequent mechanistic study, the CDA was found to be associated with reduced expression of inflammation-regulating genes involved in pathways of cytokine activity and apoptosis.22Over the past decades, evidence from small- and large-animal models has indicated that pharmacological targeting of IRI pathways is a promising strategy to attenuate IRI,21 We conducted a randomized clinical trial (RCT) that assessed the effect of a CDA modified to the clinical setting on the severity of IRI after liver transplant.Although advocated over the past decade, to our knowledge, a CDA strategy has so far not been tested in the clinic.NCT02251041) and approved by the Centre for Evidence in Transplantation. Written informed consent was obtained from study participants when they entered the transplant waiting list. The study was conducted in accordance with principles of the declaration of Helsinki23 and followed the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline. The study protocol is available in This investigator-initiated, open-label RCT (Combined Drug Approach to Prevent Ischemia-Reperfusion Injury During Transplantation of Livers [CAPITL]) with 2 parallel arms was conducted between September 2013 and February 2018, with 1-year follow-up, at the University Hospitals Leuven, Belgium. Ethical approval was obtained from the Ethics Committee Research UZ / KU Leuven and the Federal Agency for Medicines and Health Products of Belgium. Before recruitment started, the trial was registered at ClinicalTrials.gov (24) were eligible. Exclusion criteria were acute liver failure as an indication for transplant, dialysis prior to transplant, hypersensitivity or a condition with a specific contraindication to any component of the CDA  at the University Hospitals Leuven.At the time of organ offer, eligible patients were enrolled and randomized. A random allocation sequence was generated using computer-based random numbers with permuted block sizes of 2, 4, and 6. No stratification was performed on a priori–defined potential confounders such as CIT and priority on the waiting list through the Model for End-stage Liver Disease (MELD)14As part of the standard of care, all livers were preserved by static cold storage following classic organ procurement. All liver grafts were flushed with 1 L of Institut Georges Lopez (IGL-1) preservation solution through the portal vein ex situ at the end of the back-table preparation at the recipient center. All transplants were done with caval replacement using venovenous bypass. After completion of caval and portal anastomosis, reperfusion of the liver was initiated. The standard of care further included an immunosuppressive regimen consisting of tacrolimus (trough levels between 5 and 8 μg/L), mycophenolate mofetil , and steroids (tapered to 3 months).10 Drugs and doses were selected for their proven IRI-protective effects without drug-related adverse events .The primary end point was defined as the difference between the 2 study arms in peak serum aspartate aminotransferase (AST) levels within the first 72 hours after graft reperfusion, an accepted clinical surrogate of liver IRI that correlates with patient and graft survival and postreperfusion liver histological assessment.51 severity of histological IRI,52 early allograft dysfunction (EAD),53 severe postoperative surgical complications (Clavien-Dindo classification ≥3b) within the first 30 days after transplant,54 IC,55 AKI,56 acute cellular rejection,57 1-year graft survival, and 1-year patient survival  in the study.A sample size of 58 patients was needed to detect a 50% reduction in peak AST, as determined with a 2-sided, 2-sample pooled Results for the primary end point are reported for the full analysis set and a per protocol set. For secondary outcomes, the results for the per protocol set are given.58 and IRI scores. For IC and clinically relevant graft loss, the hazard ratio from a Fine-Gray model treating death without the event of interest as a competing risk is reported as well as the cumulative incidence estimates after 1 year. Death-censored graft loss and recipient mortality were visualized using (the complement of) Kaplan-Meier estimates with (exact) log-rank test. All analyses were performed from May 20, 2019, to May 27, 2020, using SAS software, version 9.4 (SAS Institute Inc). Two-sided P < .05 was considered to be statistically significant.For the primary end point, a linear regression model was used on log-transformed values with treatment group as a factor, yielding a ratio of geometric means with 95% CIs. In a sensitivity analysis, MELD score and CIT were added as confounders. The primary end point analysis was repeated in the full analysis set with exclusion of patients who received a DCD liver. Odds ratios and 95% CIs are given for the comparison of frequencies of EAD, AKI, postreperfusion syndrome, and severe surgical complications. Mann-Whitney U tests with the Hodges-Lehmann estimator as effect size were performed to compare acute cellular rejection BanffBetween September 2013 and February 2018, 310 consecutive patients were screened for the trial . Of thesOverall, the 2 study arms were balanced with respect to donor and recipient demographics and baseline characteristics . The cauP = .49) and with adjustment for these factors  . Furthermore, subgroup analysis in recipients of livers donated after brain death adjusted for CIT and MELD score did not show any difference in peak AST levels between the CDA and control groups   .There was no difference in the IRI score or frequencies of postreperfusion syndrome, EAD, severe surgical complications, IC, AKI, and acute cellular rejection between arms . OverallP = .79)  rather than a hard clinical outcome, such as primary nonfunction.Physiological differences between pigs and humans and the highly controlled and reproducible conditions of experimental models as opposed to the variability in IRI severity in the clinical setting may explain why the protective effect observed in pigs was not reproduced in this study of humans. Another factor to explain the discrepancy between the porcine model and this RCT is that the porcine study10 the CDA was also administered in situ to the donor during the flush prior to static cold storage (streptokinase and epoprostenol) as an upstream strategy (and subsequently during the transplant in the recipient as a downstream strategy) to improve the graft quality during the procurement and preservation. This more upstream strategy could not be applied in this RCT since many donor livers were imported. Of note, at the time when the RCT was conducted, dynamic preservation was still in its infancy. Therefore, a downstream strategy limited to the post–static cold storage phase may not have been sufficient to halt IRI pathways that have already been triggered or the damage that was already established as a result of the ischemic insult during procurement and preservation.11 Of note, the downstream strategy used in this RCT, which targeted the post–static cold storage graft and the graft recipient, aimed to scavenge ROS and mitigate the ensuing inflammatory cascade but was unable to achieve attenuation of IRI. The addition of an upstream strategy that prevents the formation of mitochondrial ROS by targeting the donor graft before and/or during static cold preservation may be more efficient.11 Meanwhile, the importance of maintaining the integrity of mitochondrial function and replenishment of ATP during preservation has been demonstrated in settings where ex situ normothermic64 and hypothermic oxygenated dynamic preservation65 could attenuate liver IRI.Perhaps the design of the CDA, adapted to the clinical setting, may be another plausible explanation for the difference in results. In the proof-of-concept study,33 Since α-tocopherol cannot be used clinically as an intravenous formulation, it was given to the recipient orally prior to transportation to the operative theater, and melatonin was added as a synergistic free-radical scavenger to increase the endogenous antioxidant capacity as it becomes overpowered by the burst of mitochondrial ROS after liver graft reperfusion.29 The anti-inflammatory agents glycine and mitogen-activated protein kinase inhibitor FR167653 and the antioxidant plasma protein α1-acid glycoprotein used in the porcine model are not readily available for clinical use. For this study, they were therefore replaced with infliximab, which is used as part of an immunomodulatory regimen38 in intestinal transplant to attenuate ROS production and leukocyte infiltration enhancement,40 and with recombinant erythropoietin-β to prevent apoptosis, inflammation, and oxidative stress in liver IRI.43 Antithrombin III was added to reduce microcirculatory disorders and tissue injury,37 and complement C1-inhibitor was added to reduce neutrophil infiltration and production of ROS.47 Finally, as in the preclinical model, glutathione was included to improve the vascular antioxidant capacity and hepatocyte injury as previously described,67 and apotransferrin was given to attenuate redox-active iron, which after liver graft reperfusion, is known to exceed the iron-binding capacity of transferrin and to contribute to liver graft failure.41To translate the CDA regimen from the experimental to clinical setting, changes in drug composition were made, which may also have contributed to a variability in effect. The different agents, doses, and time regimens were judiciously chosen based on published evidence of their biological efficacy and pharmacokinetics . In brie73 As a platform to deliver an upstream conditioning treatment strategy, dynamic preservation may counter or prevent ischemia and maintain mitochondria function11 and probably represents a more promising strategy than multidrug strategies targeting post–cold storage grafts and recipients only.Recent developments in liver transplantation have included significant progress in the preservation of liver grafts by using dynamic preservation strategies. Preclinical and clinical studies have shown that compared with static cold storage, dynamic preservation allows for a reduction in IRI severity, frequencies of biliary complications and EAD, hospital stay, and graft and patient survival.This study has some limitations. First, it was a single-center RCT. Second, individual effects of each component of the CDA in decreasing IRI were not assessed separately. As the CDA specifically aims to achieve synergistic effects, the parallel testing of individual drugs was considered not useful and, in the clinical setting, extremely complex given the multitude of possible combinations. Third, despite the fact that CDA components were administrated according to a specific timing in relation to their pharmacokinetic data with the aim to reach a peak concentration during reperfusion, blood levels of each component were not determined. Fourth, although the study was powered to detect differences in peak AST, the small sample size did not allow a claim on the absence of an effect.In this RCT, we did not find evidence that a combined drug approach targeting the post–cold storage graft and the recipient was sufficient to decrease IRI. Targeting the graft before and/or during preservation may also be necessary. The advent of dynamic preservation may bring the opportunity to combine a downstream CDA in the recipient with upstream conditioning of the donor liver.


Electron microscopy images suggest the phase separation of grafts to result in a network of spherical particles, due to the ability of the branched architecture to freeze chain entanglements and to bridge core domains. Small‐angle X‐ray scattering data suggest the architecture promotes the formation of multicore micelles, the core morphology of which transitions from spheres to worms, vesicles, and inverted micelles with increasing volume fraction of the grafts. A time‐resolved SAXS study is presented to illustrate the formation of the inverted phase during a polymerisation. The grafted architecture gives access to unusual morphologies and provides exciting new handles for controlling the polymer structure and material properties.We report the polymerisation‐induced self‐assembly of poly(lauryl methacrylate)‐ graft‐poly(benzyl methacrylate) in n‐dodecane. Electron microscopy and X‐ray scattering techniques are used to characterise the resulting materials.The influence of branching on polymer self‐assembly is investigated by conducting polymerisation‐induced self‐assembly of sparsely grafted poly(lauryl methacrylate)‐ The field of polymer self‐assembly has allowed the development of functional materials with wide ranging uses such as adhesives,Solution self‐assembly may be carried out in various ways, such as by using the conventional co‐solvent or film rehydration methods.In recent years, the use of complex polymer architectures for PISA has sparked some interest.graft‐poly(ethylene glycol) block to stabilise poly(cyclooctadiene) in water, resulting in a brush‐coil type architecture.graft‐poly(2‐hydroxypropyl methacrylate) and poly‐graft‐poly(diacetone acrylamide) copolymers were reported, for which only spherical micelles were found.graft‐poly(2‐hydroxypropyl methacrylate) copolymers.Moving towards grafted architectures, some research has been done at the boundary of linear and grafted polymers by using oligomeric ethylene glycolng<10 %) poly(lauryl methacrylate)‐graft‐poly(benzyl methacrylate) (pLMA‐g‐pBzMA) copolymers was conducted in n‐dodecane using the RAFT grafting from approach.block‐poly(benzyl methacrylate) diblock copolymers has been studied in detail by Armes and co‐workers, and was found to yield spherical micelles, worm‐like micelles, and vesicles across a range of block ratios. (p(LMA‐s‐HEMA)) copolymers with controlled molecular weights (Table nCTA) in each graft copolymer could be adjusted in this step with comonomer stoichiometry. Three copolymers with dissimilar degrees of polymerisation (DPs) of 206, 474, and 915 but similar comonomer ratios (11–12 mol% HEMA) were prepared to study the influence of backbone length on PISA. Conversely, three copolymers with dissimilar comonomer ratios of 2.7, 5.9, and 12 mol% HEMA but similar lengths (DP=896–939) were prepared to study the effect of grafting density. Monomer conversions were determined by 1H NMR in CDCl3 and 1 a was further isolated to collect representative 1H NMR and 1H‐13C HSQC spectra to resolve overlapping signals  and 2‐hydroxyethyl methacrylate (HEMA) was used to prepare statistical poly[(lauryl methacrylate)‐ts Table . HEMA wa1 a showed a pseudo first‐order reaction during the first 6 h . A slightly higher polymerisation rate of HEMA implied some drift in the distribution of the two monomers and therefore grafts along each chain. SEC analysis showed an increasing Mn and a decreasing dispersity with increasing conversion, indicative of a controlled polymerisation.Polymerisation kinetics of a reaction carried out under the same conditions as 1 a–5 a using the Steglich esterification method with 4‐dimethylaminopyridine and dicyclohexylcarbodiimide,1 b–5 b. 1H NMR was used to quantify CTA to LMA ratio (nCTA/nLMA), descriptive of the theoretical maximum grafting density . SEC profiles of the polymers showed a slight increase of Mn due to changes in molecular weight, solubility, and/or bulkiness of the side groups, and otherwise similar molecular weight distributions to their precursors   thermal initiator without stirring. The conversion of BzMA was determined with 1H NMR in CDCl3  of 20 wt% (wt/wt) was used in all reactions unless otherwise specified.RAFT dispersion polymerisation of BzMA from pLMA‐CTA was conducted at 70 °C in grafting from mechanism in which propagating grafts remain covalently bound to the backbone.Owing to the design of the functionalised backbones, the polymerisation of pBzMA grafts took place via the R‐group 1 b–3 b under identical reaction conditions showed the use of a long backbone to result in a more pronounced high molecular weight shoulder than using a short backbone . This may be explained by a long backbone having a higher probability of coupling per molecule, therefore affecting a larger fraction of the sample. Reactions targeting moderate graft lengths (DP 18–31) seemed to exhibit more pronounced coupling than those targeting short graft lengths (DP 1–15), despite the latter having a higher instantaneous radical concentration throughout the reaction. A possible explanation is that the self‐assembly may increase the probability of coupling by bringing propagating grafts into close proximity. Longer, more solvophobic grafts would be confined into phase‐separated globules earlier in the reaction, leading to increased coupling. This was supported by the SEC data of 10 wt% reactions showing high molecular shoulders despite the reduced backbone and initiator concentration .SEC analysis of graft copolymers prepared using backbones 1H NMR analysis showed the presence of ∼15 % uninitiated CTA even after targeting grafts with DP of 46, with reinitiation efficiency (Ieff) quickly plateauing at DP 15–25. The trend was apparent in all reactions regardless of backbone length, graft length or concentration and resulted in deviation from the targeted grafting density.Statistical variation in the graft polymerisation resulted in a considerable fraction of uninitiated side group CTAs to remain when targeting short graft lengths (Table app) and apparent grafting densities  .Polymerisations were repeated in toluene (a non‐selective solvent) to rule out effects of self‐assembly. A lognormal cumulative distribution function was fitted to data gathered across 44 PISA reactions to account for incomplete reinitiation by calculating apparent graft lengths (DP915‐CTA10%1 b targeting a range of graft lengths (DP 1–105) (Table A series of polymerisations was conducted with pLMA5) Table . The app5) Table A. WithinTEM, SEM, and cryo‐SEM imaging of the reaction mixtures revealed the presence of discrete spherical particles at the shortest and longest graft lengths  and a connected/fused regime at moderate graft lengths (DP 10) Figure A. The sp2 b–5 b. TEM of highly viscous reaction mixtures showed the presence of clustered spheres with a complex core structure , suggesting the mobility of pBzMA grafts to be a predominant factor in this transition. The formation of precipitates in 10 wt% reactions with 3 b suggested intermolecular and/or interparticle interactions to play a key role in aggregate stabilisation . Polymerisations targeting a grafting density of 29 % using pLMA194‐CTA29% resulted in coagulum even at very short graft lengths , indicating a practical lower limit for the number of pLMA units per branching point.Similar dispersion to a gel‐like transitions and TEM findings were observed for all five backbones regardless of their length or grafting density. Partial separation of solvent from the polymer phase was observed at shorter graft lengths when using shorter backbones. For backbones of similar length but different grafting density the gel‐like consistency was reached at similar graft lengths (DP≈10) as opposed to similar Q range (0.005–0.24 Å−1), thus including the size, composition, and morphology of small features but not the larger structures observed with EM  the data indicated the formation of small spheres with substantially smaller radii (16–18 nm) than the overall particle radii observed by EM (Table S4). The radii were found to increase with increasing DP, with an associated increase in radial polydispersity. An increasing inter‐sphere interaction between the pBzMA cores was indicated by the decreasing value of the “stickiness” parameter of the sticky hard sphere structure factor. This interaction could also be seen in the scattering patterns as a low‐Q. This could be due to increasing solvophobicity of the cores resulting in their further collapse, subsequently stretching of the main chain bridges, and thus a larger inter‐domain distance.A decrease in inter‐core interactions was observed at longer graft lengths (DP 10–15) as suggested by both a larger value of the “stickiness” parameter and a smaller increase in scattering intensity at low‐Q where the scattered intensity decayed at a rate of Q−1 indicating the formation of elongated cylindrical structures. The total length of these rigid cylinders could not be determined within the achievable Q range and was therefore fixed for the analysis. The findings suggested a sphere‐to‐cylinder transition to have taken place as a result of change in the packing parameterAn increase in graft length (DP 18) led to a substantial change in the scattering pattern, particularly at low‐Another large change in the scattering pattern was observed at DP 53 for which the best fit was obtained using a polydisperse vesicular form factor. The vesicle wall thickness was found to be smaller than the diameter of the cylindrical micelles (Table S6), suggesting greater interdigitation of chains within the bilayer.50, 51Q range resulted in a lack of an observable Guinier region and therefore the accuracy with which the total radius could be defined by SAXS was limited. Given the stability of these particles in solution, a substantial surface fraction of pLMA must remain. This was supported by the fitting parameters which suggested 25 % of the particle surface to consist of pLMA.Graft DP 105 showed a further change in the scattering pattern. The best fits to these data were obtained with a model describing a large sphere consisting of a pBzMA continuum with smaller spheres of pLMA situated within, implying phase inversion to yield an inverted multicore micelle. With pBzMA now forming the continuous phase within the particle and giving a good contrast against the solvent, the overall particle size and shape could be observed (Table S7). While the total particle radius was found to be close to that observed by TEM , the restricted To learn about the transitions leading up to the inverted multicore micellar structure, the polymerisation targeting DP 105 graft was repeated in a time‐resolved SAXS experiment to monitor morphological transitions in situ. Data was collected continuously over 320 min at 70 °C and binned to a 5‐minute time resolution  and an increase in zero‐angle intensity (I0) were consistent with the growth of the grafts . These differences were ascribed to differences in backbone concentrations and therefore chain entanglements, the presence of BzMA in the solvent phase affecting the solubility of grafts at low conversions, and/or measurement temperature.The scattering patterns collected over the first 50 min showed no self‐assembly and suggested that individual molecules remained as Gaussian chains. The increasing radius of gyration  should be addressed to the authors.Supporting InformationClick here for additional data file.