To understand the current situation and progress of nursing students’ professional self-concept, this review aimed to perform a general analysis of research related to the connotation of professional self-concept, measurement tools, influencing factors, effects, and intervention experiments.Three databases  were searched for relevant articles. Research articles that met specific criteria were included, with identified articles initially screened by title and keyword. Then the abstracts were screened for relevance, and the full text was read for validation before inclusion. Descriptive analysis was performed with relevant findings from data retrieved from various sources.Finally, 54 articles that met the criteria were included, which organised the connotation of self-concept of nursing speciality, and introduced six measurement scales, such as Professional Self-Concept of Nurses Instrument and Nurse’s Self-Concept Questionnaire. A total of 16 investigations on influencing factors were described, and the results showed that there were internal individual and external environmental factors. The professional self-concept was formed by analysing both factors. This paper described 17 effect surveys and found that professional self-concept had an important impact on students’ mental health, academic performance, and professional values, and so on. Eight intervention experiments including attribution training and hierarchical teaching were evaluated.Research articles on the professional self-concept included in this review were rich. These articles clarified the basic connotation of the concept, developed relatively mature measurement tools, found many influencing factors and effects, and proposed effective intervention strategies. They were of great value for understanding the professional self-concept and could provide a reference for scholars to conduct relevant research and practice. It also presents research prospects in this field, aiming to inspire future research. The World Health Organization designated 2020 as the ‘International Year of the Nurse and the Midwife’ to recognise the important contributions made by these practitioners to global health. Nurses, as an important workforce in health services, have received increasing attention. As future nurses, nursing students’ professional self-understanding will have a crucial impact on their practice  and is sThis review includes a systematic search, research review, and descriptive analysis of existing literature.In September 2021, three databases, Web of Science, PubMed, and Child National Knowledge Infrastructure (CNKI), were searched using ‘professional self-concept of nursing student’ or ‘nursing students’ professional self-concept’ as key terms.The following inclusion criteria were used: describing nursing students’ professional self-concept theory, measurement tools, influencing factors, effects, and intervention experiments. The following exclusion criteria were used: unrelated to the subject matter, the same or similar to previous studies, and omitted data.A total of 1244 papers were obtained using the aforementioned search method, and duplicate papers were deleted. The authors screened the remaining papers to evaluate their relevance. Only those related to the research purpose and that met the inclusion criteria were included. We screened the abstracts of articles with relevant titles, and if deemed applicable, the full text was retrieved and reviewed. A total of 47 articles were selected for further analysis. Considering the continuity of theoretical development, we screened the list of references and searched the important literature on ‘self-concept’ and ‘professional self-concept’ manually. Based on this, seven additional articles were selected. Thus, 54 articles were included . The firMicrosoft Excel was used to create a data chart describing the literature on the measurement tools. Data were extracted independently from the articles and classified according to the following headings: title, author, compilation time, initial sample, scoring method, dimension (entry type), and internal consistency. A data chart describing the literature on the influencing factors was also created. Data were extracted independently from the articles and classified according to the following headings: author, title, publication year, research country, research type, number of participants, data collection time, and main research findings. To understand the quality of the intervention research in detail, the bias risk assessment and internal authenticity evaluation of the literature included in the intervention experiment were conducted using the risk of bias (RoB) 2.0  and the We conducted a general analysis of the research on nursing students’ professional self-concept by combining all the relevant findings from the data retrieved from various sources, and systematically describing the concept connotation, measurement tools, influencing factors, effects, intervention means, and so on to evaluate the existing research status and confirm the knowledge gap, which can provide a reference for future research.The idea of ‘self-concept’ was proposed in the continuous enrichment of the understanding of the ‘self’, and subcategories such as ‘academic self-concept’, ‘social self-concept’, and ‘professional self-concept’ were subsequently developed . AccordiConnotation of self-conceptSelf-concept refers to the relatively persistent self-experience and perception of an individual’s self-existence, a coping style appropriate to their environment , and a pConnotation of professional self-conceptProfessional self-concept is a subordinate concept of a specific component of self-concept that has a significant impact on behavioural achievements in professional fields and can predict individual professional achievements. It is a subjective process wherein individuals understand, apply, and enrich their self-concept for professional development. It is an attitude, morality, ideal, sense of responsibility, values, and so on toward the individual’s profession, which is generated based on gradual understanding . In his Connotation of professional self-conceptThe cultivation of students’ strong positive self-concept has been highly valued since nursing students’ self-esteem, self-confidence, and their influence on career choices received attention . The proThe proposal of self-concept is conducive to better grasping individuals’ self-understanding from social, psychological, and environmental perspectives. However, a high degree of abstraction of concepts impacts specific applications, and corresponding measurement tools need to be developed to facilitate the feasible application of concepts. Tennessee Self Concept Scale (TSCS), Wallance Self-Concept Scale (WSCS), Self-Description Questionnaires (SDQ), Multidimensional Self Concept Scale (MSCS), and other tools were subsequently introduced. The development of these scales also enabled nursing students to develop a measurement of their professional self-concept.Professional self-concept of nurses instrumentDavid Arthur of Hong Kong Polytechnic University developed the Professional Self-Concept of Nurses Instrument in 1995. The scale included nursing diploma students in New South Wales, Australia, as a sample. Upon interviewing 24 graduating students and consulting nursing teachers and experts, a multi-dimensional structural model was established, and a questionnaire with seven dimensions and 56 items was initially completed. To test the questionnaire, 170 junior nursing diploma students in that region were selected as survey participants. Through structural analysis, factor analysis, and reliability evaluation, a formal scale comprising 27 items, including ‘practical skills ’, ‘satisfaction’, and ‘communication’, was developed, with a contribution rate of variance of 40.5% . The scaNurse’s self-concept questionnaireBased on the multi-dimensional and multi-structural theoretical model proposed by Shavelson et al., Leanne Cowin, from Western Sydney University, developed Nurse’s Self-concept Questionnaire (NSCQ) in 2001. In this study, six-month informal interviews were conducted with clinical nurses in Sydney, Australia. Entries were extracted by encoding the qualitative interview data, and then reviewed and revised by an expert panel comprising six nursing experts and three self-concept experts. Initially, a preliminary questionnaire with 80 items was formed. It was used to investigate clinical registered nurses and nursing graduate interns from six major nursing colleges in Sydney. A total of 2118 individuals participated in the survey. Exploratory and confirmatory factor analyses were performed on the results, and a formal questionnaire with 36 items in six dimensions  was developed, with a variance contribution rate of 72.9% . HosseinNurses’ self-concept instrumentElizabeth Angel of Western Sydney University focused on the possible differences caused by cultural diversity in nurses’ professional self-concept among international students, specifically those from highly collectivist countries and local students. Referring to the NSCQ scale, she developed the Nurses’ Self-Concept Instrument (NSCI). This study selected 218 local and 35 international nursing students from an Australian university. The scale contains 14 items across four dimensions: care, knowledge, colleague relationships, and leadership. It could better clarify specific differences in the self-concept of specific cultural groups regarding cross-cultural analysis .Other Relevant Measurement ToolsMoreover, according to the core connotation of nursing professional self-concept, tools such as Nurse’s Self-Description Form (NSDF) and the Porter Nursing Image Scale (PNIS) can also provide reference and enlightenment for us to measure nursing professional self-concept ,22 Tabl.Table 1The development of measurement tools has improved the feasibility of follow-up research on this concept. Hence, an empirical investigation of the professional self-concept of nursing students has been widely conducted. While measuring the status, many influencing factors were revealed.Individual factorsRegarding individual factors, Yoo (2019) found that interpersonal relationships, positive psychological capital, religious beliefs, and learning performance affect the professional self-concept of nursing students . CoPlu eEnvironmental factorsRegarding environmental factors, Chang (2021) showed that the cultivation of critical thinking, a sense of belonging, and campus culture could continuously promote the development of nursing students’ professional self-concept . FangfeiIn the empirical study, nursing students’ professional self-concept was studied as ‘result variable’, ‘dependent variable’, and ‘intermediary variable’ to explore the related effects and understand the impact on student development.Influential effectRegarding student psychology, Ge et al. (2020) surveyed 304 nursing students of different educational backgrounds in China and found that the definition of self-concept could positively affect students’ empathy . Zhang eRegarding student learning, Jahanbin et al. (2012) found in a study of 60 senior nursing students in Iran that the professional self-concept of students could significantly promote clinical performance . Shin etRegarding professional values, CoPlu et al. (2018) found that nursing students’ professional self-concept had a positive impact on professional values through a survey of 619 senior nursing students in Turkey . Bi et aIntermediary effectThrough a cross-sectional survey of 294 nursing students in South Korea, Hyun et al. (2018) found that professional self-concept played a role in increasing the impact of teacher-student interaction on job search anxiety, and there was a significant intermediary effect between the two . AnotherAs professional self-concept plays an important role in student development, attention has been paid to cultivating nursing students’ positive professional self-concept, and experimental studies on related interventions have become increasingly abundant. The analysis of experimental results and evaluation of methodologies help provide evidence for future intervention practices.Implementation of intervention experimentsPu (2009) conducted a randomised controlled trial of 128 Chinese nursing interns and found that the experimental group using the reflective learning model had higher scores regarding professional self-concept . Hensel Evaluation of research qualityThe RoB 2.0, bias risk assessment tool and evaluation manual of the Australian JBI Evidence-based Centre were used to evaluate the quality and authenticity of the aforementioned eight experimental research articles and assess the bias risk. Four randomised controlled trials (RCTs) ,56–58 weExisting research shows that the theory of professional self-concept for nursing students has been well developed under the overall framework of self-concept and its connotation, characteristics, and significance have been explained. Its multi-dimensional and multi-factor structural characteristics conform to the research orientation of psychometrics. Research on related measurement tools has rapidly developed. Hence, a solid foundation for research on the professional self-concept of nursing students was laid and related empirical research was conducted extensively. The influencing factors varied, namely, internal individual and external environmental factors. Under their combined effects, nursing students develop their professional self-concept. It exerts an important influence on students’ mental health, academic performance, and professional values, which is significant for their development. The experimental results prove that schools can effectively intervene in students’ professional self-concept through some explorations of reform; however, due to the limited quantity and quality of original studies, it is difficult to conduct an evidence-based evaluation. More evidence is required to support this conclusion. It can be seen that the professional self-concept is important and can be measured. Hence, it has attracted the attention of scholars. By combining existing research, we have also identified some aspects that need to be added.Cultural background and race may affect specific aspects of professional self-concept to promote or prevent professional behaviour . A crossThe development of self-concept is a dynamic process subject to the constraints of age and cognitive development. Nursing students’ professional self-concept was dynamic. It undergoes constant change with an in-depth study of courses and the impact of the internship . It is aNursing education is necessary and can cultivate students’ strong professional self-concept . It is iScientific research must be conducted using sound theoretical systems and profound theoretical accumulation. Future research on nursing students’ professional self-concept can be furthered in the following four aspects: First, strengthen the study and delve into existing research. Research on nursing students’ professional self-concept has a history of more than 30 years. The theoretical accumulation of research can be further enriched through in-depth research on previous literature, and that can be conducted more deeply based on communication with previous researchers. Second, the interpretation of concepts from different national and cultural backgrounds should be emphasised. Affected by multiple factors, such as medical level, health insurance strategy, and health service pricing, there are significant differences in nurses’ professional development levels, career development paths, and practice restrictions in different countries. It is necessary to understand students’ specific understanding from different cultural backgrounds and social environments. Third, we explored the influence mechanism. The professional self-concept of nursing students is systematically affected by a combination of internal and external factors. The significance of conducting only the confirmatory single-factor test is limited. Multiple factors should be considered when exploring the mechanism of this effect. Fourth, comprehensive and effective intervention strategies must be developed. Professional self-concept significantly impacts student development. Comprehensive and effective intervention strategies should be designed and experimentally verified. Hence, evidence-based evaluation can be conducted to provide more high-quality evidence and a reference for scientific intervention.Research articles on the professional self-concept included in this review were rich. These articles traced back to the development of research on professional self-concept of nursing students, clarified the basic connotation of the concept, developed relatively mature measurement tools, found many influencing factors and effects, and proposed effective intervention strategies. They were of great value for understanding the nursing students’ professional self-concept and could provide a reference for scholars to conduct relevant research and practice. At the same time, this review also proposes some areas for improvement in this research field, including ‘paying attention to different cultural backgrounds’, ‘exploring specific impact mechanisms’ and ‘improving the quality of evidence for intervention’. It also presents research prospects in this field, aiming to inspire future research.


Mycophenolate mofetil (MMF) is a prodrug of mycophenolic acid (MPA) and a key immunosuppressant for improving graft survival in patients with heart transplantation (HTx). However, dose reduction or interruption is occasionally needed due to gastrointestinal (GI) side effects. Enteric-coated mycophenolate sodium (EC-MPS) is an alternative form of MPA delivery to improve GI tolerability. In the present study, the efficacy of EC-MPS compared with MMF in HTx patients was investigated.In this retrospective study, the Korean Organ Transplant Registry (KOTRY) data were used to analyze the efficacy and rejection rate of MMF and EC-MPS. A total of 611 patients was enrolled from 2014 to February of 2021. Patients were divided based on the use of MMF or EC-MPS at 6 months post-HTx. Patients who were not prescribed MMF or EC-MPS were excluded. Graft survival, all-cause mortality, and treated rejection were compared between the two groups. All statistical analyses were performed using SPSS; characteristics were compared using Pearson chi-square test and survival rate with Kaplan-Meier plot and log-rank test.A total of 510 HTx patients was analyzed . At 6 months after HTx, 78 patients were taking EC-MPA (12.8%) and 432 patients were taking MMF (70.7%). The median follow-up was 42.0 months (IQR: 21.7–61.0 months). Post-HTx outcomes including overall survival, all cause mortality, acute cell mediated rejection (ACR), acute antibody mediated rejection (AMR), treated rejection, and cardiac allograft vasculopathy (CAV) were comparable between the two groups during follow-up.Notable differences were not observed in overall survival, all cause mortality, ACR, AMR, treated rejection, and CAV between MMF and EC-MPS groups. Efficacy of EC-MPS was similar to that of MMF in HTx patients during mid-term follow up after HTx. Heart transplantation (HTx) is the standard treatment for end-stage heart failure (HF). Survival and prognosis of HTx have improved over the last two decades with introduction of effective immunosuppression therapy , 2. Gene®, Novartis Pharmaceuticals, East Hanover, NJ, USA) was developed to reduce GI effects of MMF. Clinical trials in kidney transplant recipients demonstrated that EC-MPS is therapeutically equivalent to MMF  is a potent anti-proliferative drug that recently replaced azathioprine as the drug of choice due to improved survival and reduced rejection rates compared with azathioprine . MMF is t to MMF , 8.Unlike kidney transplantations, data regarding long-term HTx outcome with use of EC-MPS are limited. In the present study, using a nationwide organ transplant registry in Korea, post-HTx outcome was evaluated between patients taking MMF or EC-MPS in combination with CNIs and corticosteroids.The nationwide multi-center HTx data submitted to the Korean Heart Transplant Registry (KOTRY), the first nationwide organ transplantation registry in Korea, was used in the present study . From 20CNI-based triple immunosuppressive therapy  was initially administered as maintenance therapy to most patients. Cyclosporine was administered if patients developed severe side effects from tacrolimus, such as seizures or encephalopathy. A regimen using a mammalian target of rapamycin (mTOR) inhibitor, either sirolimus or everolimus, in place of a CNI-free regimen was prescribed to eligible patients, including those with renal insufficiency or malignancy. An mTOR inhibitor was administered in conjunction with a CNI in patients who developed rejection with graft dysfunction, cytomegalovirus infection, or cardiac allograft vasculopathy (CAV). In case of intolerance to an mTOR inhibitor, a conventional CNI-based regimen was maintained. Patients at low risk of rejection were tapered off steroids 6 months after HTx according to transplantation clinic protocol. All HTx recipients underwent a protocol-based regular evaluation at their transplantation clinic . Post-HTContinuous variables are recorded as mean ± standard deviation, and categorical variables are reported as frequency and percentages. Baseline recipient/donor characteristics and clinical outcomes of HTx were compared between MMF and EC-MPS groups. Post-HTx outcomes included treated rejection and all cause mortality. The two groups were compared using chi-square test, and continuous variables using Student's t-test. The cumulative incidence of events and outcome analysis was assessed using the Kaplan-Meier method, and statistical significance was calculated using the log-rank test. Due to the number difference between the two groups, 1 to 1 individual matching within caliper by propensity score matching was performed. Analysis by chi-square test was used for group comparison, and two sample t-test was used for continuous variables. All data were analyzed using SPSS version 25.0  and R-version 4.2.0 .p = 0.031). In addition, significantly more patients  in the EC-MPS group remained on steroid treatment at 6 months post-HTx compared with subjects in the MMF group. An average dose of 1,500 mg  of MMF and 1,080 mg  of EC-MPS was used in each group. This amount is an equivalent dose of the active form, MPA.Among the 510 HTx patients, 432 were taking MMF (70.7%) and 78 were taking EC-MPS (12.8%) post-HTx. Patients in EC-MPS group were younger and had longer warm ischemic time, aortic-cross clamp, and cardiopulmonary bypass time . Signifip = 0.049) experienced treated rejection during the first year compared with the MMF group, graft survival and overall survival were comparable between two groups. During follow-up, incidences of an infection requiring hospitalization were similar between the two groups.Significant differences in all-cause mortality and freedom from treated rejection were not observed between the two groups  during tWe performed a subgroup analysis of patients treated with cyclosporine, because cyclosporine is known to influence MPA pharmacokinetics. Post-HTx clinical outcomes were comparable between MMF and EC-MPS group in subgroup of patients who were treated with cyclosporine .Due to significant difference of baseline characteristics between MMF and EC-MPS groups, a propensity score matching analysis was conducted with adjustment of age, gender, pre-HTx ECMO and prolonged steroid use . In thisTo the best of our knowledge, this is the first mid-term study in which post-HTx outcomes from a multi-center registry were compared between patients receiving MMF or EC-MPS. During the mean follow-up of 40 months, post-HTx clinical outcomes were similar between MMF and EC-MPS groups, although significantly more patients with EC-MPS experienced treated rejection at 1-year follow-up.MMF, due to its effectiveness in reducing acute rejection rates , is now de novo trials, similar safety and efficacy of EC-MPS compared with MMF were observed in kidney transplant patients with similar rejection, infection, and graft survival at 12 months post-kidney transplant  and 12 months (57.7 vs. 60.5%) , 22 postThe present study had limitations due to the retrospective design and the different number of subjects in the MMF and EC-MPS groups. Data regarding MPA level were lacking, as this is not a routine practice in many centers. Time-dependent dose change of MMF and EC-MPS might not have been reported due to pre-specified follow-up intervals in the KOTRY registry and other immunosuppressive regimens determined based on the protocol of each transplantation clinic.The main use of EC-MPS being an alternative for MMF intolerance due to its gastrointestinal side effects, and this study might been more profound if the actual incidence and severity of GI side effects was assessed after HTx. Unfortunately, due to the nature of our retrospective study, the severity and rate of intolerance were not consistently assessed with objective tools in this registry, therefore, difference in gastrointestinal complications between two groups could not be provided. However, the present study is valuable because our study described and compared real world post-HTx clinical outcomes between MMF and EC-MPS groups from a multi-center, nationwide registry.In conclusion, HTx patients treated with EC-MPS and MMF have similar incidence of overall survival, ACR, AMR, treated rejection, CAV, and all cause mortality. Mid-term post-HTx clinical efficacy of EC-MPS was similar to that of MMF in HTx patients.Relevant data are available from the corresponding author on reasonable request.The studies involving human participants were reviewed and approved by KOTRY. The patients/participants provided their written informed consent to participate in this study.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.This research was supported by a fund  by Research of Korea Centers for Disease Control and Prevention Agency. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Curcumin has multiple properties that are used to cure different diseases such as cancer, infections, inflammatory, arthritic disease, etc. Despite having many effects, the inherent physicochemical properties—such as poor water solubility, chemical instability, low bioavailability, photodegradation, fast metabolism, and short half-life—of curcumin’s derivatives have limited its medical importance. Recently, unprecedented advances in biomedical nanotechnology have led to the development of nanomaterial-based drug delivery systems in the treatment of diseases and diagnostic goals that simultaneously enhance therapeutic outcomes and avoid side effects. Mesoporous silica nanoparticles (MSNs) are promising drug delivery systems for more effective and safer treatment of several diseases, such as infections, cancers, and osteoporosis. Achieving a high drug loading in MSNs is critical to the success of this type of treatment. Their notable inherent properties—such as adjustable size and porosity, high pore volume, large surface area, functionality of versatile surfaces, as well as biocompatibility—have prompted extraordinary research on MSNs as multi-purpose delivery platforms. In this review, we focused on curcumin-loaded silica nanoparticles and their effects on the diagnosis and treatment of infections as well as their use in food packaging. In the past few years, several investigations have focused on applying mesoporous silica-based platforms as efficient nanocarriers . There aIn general, MSNs have more long-term release in comparison with organic nanoparticles, because prodrugs can be trapped inside their nano-pores. However, if pro-drugs were trapped in organic nanoparticles, the organic substance would rapidly degenerate; because of the quick pro-drug release . The nanThe promising properties of mesoporous inorganic materials, particularly MSNs, are easily adapted to incorporate and interact efficiently with a range of low-solubility medications and biomolecules . TherefoThrough the functionalization of silica nanoparticles with different coating agents, the loading can be more controlled. As untreated silica nanoparticles have been known to be highly negatively charged and have stable hydrodynamic sizes in a wide pH range, by controlling the surface charge of colloidal silica nanoparticles, a positively charged surface can be formed. Many coating agents—such as amine-containing molecules, multivalent metal cation, or amino acids—can be applied to positively treat the silica nanoparticles. Moreover, molecules with chelating sites have shown high affinity with the silica surface to produce gel-like networks. Amino acid coatings also can be resulted stable silica colloids . MSNs haClinical medicine has many medicinal products for therapeutic applications, and with a greater understanding of the molecular mechanisms of disease, this list is growing rapidly. Several herbal agents have low water solubility, and this is generally related to low oral bioavailability . For devCurcuma longa plant is curcumin. It is composed of small natural molecular weight yellow-orange polyphenol, which has been used in wound healing, diabetes, and cardiovascular disease due to its outstanding antibacterial, anti-inflammatory, and antitumor activities [One active substance that is found in the roots of the tivities ,13,14,15A hopeful methodology to overcome systemic toxicity and low bioavailability is the application of nanocarriers, such as liposomes, polymeric nanoparticles, micelles, and dendrimers ,17,18. TBesides proper surface properties, MSNs have good biocompatibility, easy surface modification, controllable size, etc., making them exceptional candidates for different medical applications ,22,23. DThis is the first review to consider MSNs as the carrier for curcumin for the diagnosis and treatment of infections, as well as considering their applications in the food industry. The necessity for such a review is a consequence of rapid progress in this field. This review may help investigators accelerate studies and development of this essential field of nanomedicine and, eventually, industrial and clinical applications.Plants are important natural resources for the preparation of medicinal products for various therapeutic purposes ,27,28,29Silica nanoparticles (SiNPs)—with vital benefits such as large surface area, simple functionalization, and biocompatibility—are one of the most frequently applied nanoparticles in drug delivery uses. A porous model, mesoporous silica nanoparticles (MSN), also shows additional features such as tunable pore size and volume, leading to high drug loading volume ,44. The 2 used in the production of the nanoscale SiO2 include organo silicates, silanes, chlorosilanes, tetraethylorthosilane, and waste ash from biomass.There are different kinds of MSNs with different properties and applications . Table 3First, the ability of MSNs to inter the bacteria and biofilm has been illustrated, then the challenge is in fighting antibacterial resistance by designing nanosystems with improved antimicrobial effectiveness through combining different antimicrobial components in the same nanoplatforms. For this purpose, various studies have identified innovative strategies based on shared delivery of antibiotics or combining antibiotics and antimicrobial metal nanoparticles or ions ,67.S. aureus (24 h) and E. coli (72 h), attributed to the increased impact of the bactericide of curcumin and silver nanoparticles [Concerning the first approach, the easiest way is to load different antibiotic molecules into the MSNs’ pores at the same time. The co-loading of agents with different—and sometimes conflicting—physicochemical properties in 26-side a single MSN requires development of compartmentalization approaches. One of the interesting methods for co-delivery of therapeutic agents of different chemicals is the use of MSNs with asymmetric structure and anisotropic geometry and two compartments that can load drugs of different natures in separate storage spaces. Song et al. decorated silver nanoparticles in mesoporous silica of SBA-15 covered by melanin-like polydopamine (PDA) as carriers. During this time, the constructed mesopores were charged with curcumin (CCM) by their noncovalent connections with coatings of PDA. The acquired CCM@SBA-15/PDA/Ag compounds were characterized physiochemically and demonstrated low hemolytic action and positive biocompatibility . Realiziarticles .3O4@SiO2&EPMO (EPMO = ethane bridged periodic mesoporous organosilica) was extended effectively through an anisotropic epitaxial growth approach. The absorbance measurement at 600 nm evaluated the antibacterial effects of Fe3O4@SiO2-GS&EPMO-Cur. S. aureus and E. coli were selected as bacterial models. At the same concentration, Fe3O4@SiO2&EPMO-Cur and Fe3O4@SiO2-GS& EPMO-Cur have a better antimicrobial effect than curcumin, because of the enhanced solubility of curcumin loaded with the asymmetric lollipop-like nanoparticles. The rising concentration of curcumin, Fe3O4@SiO2&EPMO-Cur, and Fe3O4@SiO2-GS&EPMO-Cur caused the viability of E. coli and S. aureus to decrease considerably. In addition, Fe3O4@SiO2-GS&EPMO-Cur shows that it has much more capacity for inhibiting bacteria than Fe3O4@SiO2&EPMO-Cur in the same concentration. This is due to the synergic effect of curcumin and gentamicin concurrently loaded into the asymmetric lollipop-like nanoparticles [Asymmetric MSNs with dual-compartments and anisotropic geometry are very desirable for charging and releasing dual drugs into separated storage areas. In a study, an asymmetric lollipop-like mesoporous silica nanoparticle Fearticles .The antibacterial activity of curcumin on Gram-negative and Gram-positive species has been demonstrated. Cheng and coworkers designed novel core–shell magnetic MSNs. Curcumin and gentamicin were separately loaded into the hydrophobic and hydrophilic spaces to provide dual anticancer and antibacterial nanosystems .E. coli [E. coli and S. aureus, which was evaluated by the disk diffusion test [S. aureus was more than E. coli; however, the antibacterial activity of chitosan with curcumin was more than the nanocomposite film [A trio-hybrid nanocomposite of MSNs including copper, loaded with curcumin and decorated with Ag nanoparticles, represented the photokilling of E. coli . The nanE. coli . A nanocion test . It has ite film .S. aureus (MRSA) were represented by hybrid nanofiber mats in vitro [To combine the benefits of polyvinylpyrrolidone (PVP) with MSNs, Li et al. have designed a hybrid hemostatic organic–inorganic material using electrospinning by integrating the curcumin-loaded MSNs (CCM-MSNs) into PVP nanofiber mats . Furtherin vitro .Curcumin is loaded into already prepared mesoporous silica nanoparticles and the resultant complex is introduced into a PVP (polyvinylpyrrolidone) solution. Electrospinning of the admixture leads to the drug arrangement into suitable positions of the polymer results in the production of hybrid PVP-based curcumin-loaded mesoporous silica nanofibers mat.E. coli. SNPs were decorated over the surfaces of Cu-MSNs by coordination of silver ions on diamine-functionalized Cu-MSNs and with formalin further reduced to silver nanoparticles. The ability of silver in sensitizing E. coli as a specific phototherapeutic agent in vitro was shown, so it can expand the phototherapeutic spectrum of curcumin. After external decoration with silver nanoparticles, and following loading of curcumin, the mesoporous structure of Cu-MSNs remains intact. Various physical characterization techniques have confirmed the synthesis and successful assembly of the functional nanomaterials. Under light irradiation, curcumin may produce large quantities of ROS, which may enhance the kinetics of silver ion release for antimicrobial activity. Cu-MSNs positive-laden modified surfaces support antimicrobial response by electrostatic attractions to negative-load bacterial cell membranes.Kuthati et al. prepared copper-loaded MSNs (Cu-MSNs) with immobilized silver nanoparticles (SNPs) for applying photodynamic inactivation (PDI) to drug-resistant A synergic mechanism for transferring energy of the absorbed light from SNP to curcumin may activate the antibacterial effect of the prepared nanocomposites . Vallet-First, bacteria that are present in infections of bone-implant (both in the planktonic and biofilm forms) should be locally destroyed in situ to prevent the need for surgical procedures for removing and replacing prostheses that were infected by bacteria. In contrast, in the infected area, antimicrobials—which may contain only antibiotics or the combination of metal ions and antibiotics—must be treated with small, high-specificity doses to enhance their efficiency and decrease dangerous side effects in healthy cells, tissues, and organs.This aim can be achieved via nanocarriers capable of charging, protecting, and transporting antimicrobial agents to the target . Upon arrival, the nanocarriers gradually release antimicrobial agents in response to specific external or internal stimuli. Among nanosystems, MSNs came as the third item that meets all those demands. In this way, innovative and advanced technologies are used in the design and development of advanced targeted stimuli-responsive MSNs-based nanocarriers for antimicrobials administration.p > 0.05). In each group, inflammatory responses impressively decreased by day 21 of treatment, the procedure of angiogenesis was nearly complete by day 7, wound reepithelization with a high degree was accomplished by day 21, and fibroblast proliferation significantly grew by day 14, without significant contrasts between the groups. Through day 21, the collagen level substantially extended in rats that had been treated with the curcumin nanoformulation as compared with the control group.It has been demonstrated that curcumin can tweak physiological and molecular occasions included in the inflammatory and proliferative stages of the wound healing process . CurcumiS. aureus and P. aeruginosa. The photodynamic therapy (aPDT) effect on the planktonic and biofilm forms of bacteria was investigated at 465 nm.Mirzahosseinipour et al. studied the antibacterial photodynamic impact of curcumin silica nanoparticles and free curcumin as photosensitizer agents on planktonic and biofilm forms of S. aureus and P. aeruginosa. It was concluded that if they use curcumin in the form of curcumin-silica nanoparticles, there would be a decrease in the amount of producing bacterial biofilm and the number of bacteria in planktonic states. Curcumin-silica nanoparticles displayed a wound healing effect in the scratch assay in vitro [One of the major issues in public health is the multidrug resistance of pathogenic bacteria. Subsequently, finding new techniques for fighting multidrug-resistant bacteria has become increasingly urgent. One forward-looking method is antimicrobial aPDT, which includes utilizing photosensitizer and nontoxic dyes, which are stimulated by visible light and produce oxygen-free radicals. In one study, researchers analyzed the antibacterial photodynamic activity of curcumin silica nanoparticles and free curcumin as photosensitizers on planktonic and biofilm forms of in vitro . Xi et aMultifunctional bioactive PPCP nanofibers matrix offers a competitive technique for wound healing induced by skin cancer and bacterial infections .Bacillus subtilis and E. coli strains displayed an enhanced inhibition area. Research on Wistar rats via engineered nanofibers included with amine-functionalized SBA-15 and curcumin confirmed 99% scar-less wound recovery in 21 days.Rathinavel et al. produced a composite nanoscaffold that has potential in wound healing therapeutics and contains curcumin, SBA-15 (Santa Barbara Amorphous), and amine-functionalized SBA-15 polycaprolactone (PCL). The excessive biocompatibility and cell adhesion of amine-functionalized SBA-15 and the extensively investigated antimicrobial effects of curcumin included advantages for wound healing. Antibacterial studies carried out on The results of Masson’s tri-chrome and hematoxylin–eosin staining displayed tissue re-epithelialization, formation of granulation tissue, and collagen deposition. The fabricated nanoscaffold could be an efficient system for wound healing . In anotThe results of cell adhesion, MTT assay, and live/dead assay indicate that the nanoscaffold had a higher rate of biocompatibility, cytocompatibility, proliferation, and cell migration without toxicity on cells. The synthesized nanofiber forms a powerful nanomaterial for the treatment of skin wounds.In the end, the results of in vivo study showed that SBA-15-incorporated PVA nanofiber with curcumin appeared to possess effective wound healing effects .Several investigations have been performed to study the antiviral potential of the herbal compound due to the lack of prevention and treatment options for numerous viral infections ,80. The 3+ and Eu3+. The experimental work was divided into two parts. Firstly, MSNs were synthesized with a temperature-controlled release feature and dual-imaging function with final loading through curcumin. Once formed, the dual imaging function (MSN-EuGd) can be achieved by calcination for pattern removal. Curcumin was loaded after surface modification. Secondly, curcumin-loaded mesoporous silica nanoparticle composite was compared with free curcumin for antivirus capability. Finally, the drug carrier with temperature-controlled features and dual imaging function was synthesized for inhibition of the Zika virus [Lo et al. designed a temperature-controlled and dual imaging drug carrier that prevents Zika virus infection when loaded on curcumin . High feka virus .The PEGMA surface-modified EuGd-based mesoporous silica nanoparticles act as a temperature-controlled gatekeeper. When the temperature rises above 39 °C, the PEGMA turns into a coil that leads to the opening of the gate. Then, curcumin loads into the MSN pores. On another hand, when the temperature drops below 39 °C, the PEGMA becomes globular in shape over drug-loaded nanoparticles and closes the gate . Listeria innocua as a foodborne human pathogen was completely inhibited via PVA-SNP-ba films. The bacterium was reduced by 2.5 log using curcumin-loaded PVA-silica nanoparticles. Furthermore, the curcumin-loaded PVA-silica nanoparticles-based film displayed a 16 mM/g antioxidant effect as compared to 14.6 mM/g of PVA-silica nanoparticles-ba. Such an approach as the one described could be used as a scaffold for the fabrication of PVA-based packaging materials as an active alternative to silica. Thus, the safe entrapment of bioactive candidates with such biodegradable films could be valuable in both medicine and food industries [Recently, packaging materials with advanced technology have become a topic of great scientific and practical interest ,88. Formdustries .E. coli and S. aureus. These results suggest that the CS/SBA-15-Cur nanocomposite film can be a promising material for food packaging [In another study, to improve the functional properties of pure chitosan film, curcumin-loaded mesoporous silica nanoparticles (SBA-15) were inserted into chitosan (CS) film. Curcumin was loaded into SBA-15 (SBA-15-Cur) via the Rotator technique. The CS/SBA-15-Cur nanocomposite film was prepared by solvent casting . The SBAackaging .Salmonella detection in fluorescent and colorimetric dual-modal sensing.Nanomaterials are widely utilized in the development and improvement of biosensor properties ,92,93. MS. typhimurium to immunize MSNs@CUR@ZnO@pAbs nanoparticles will be achieved. The S. typhimurium cells, the immune magnetic nanoparticles (MNPs), and the MSNs@CUR@ZnO@pAbs NPs were conjugated in the microfluidic chip with a Koch fractal mixing channel to form MNPs-bacteria-MSNs@CUR@ZnO@pAbs complexes. Lastly, acetic acid (HAc) was introduced to release curcumin from the complexes, and both the fluorescence and color changes were evaluated to determine the bacterial concentration. This designed biosensor was capable of quantitatively identifying S. typhimurium, ranging in 1.5 h from 102 to 107 CFU/mL [MSNs were initially incubated with curcumin to reach MSNs@CUR (MC NPs). It was then coated with ZnO nanoparticles to form MSNs@CUR@ZnO nanoparticles to inhibit the premature release of curcumin, followed by modification with polyclonal antibodies (pAbs) against 7 CFU/mL .In this study, the applications of silica nanoparticles with curcumin in the treatment of bacterial infections, food packaging, and the diagnosis of bacterial infections were investigated. These phytochemical silica nanoparticles with tremendous benefits—such as exceptional biocompatibility and cost-effective preparation—can be used as promising nanostructures to treat and diagnose infections. Because sufficient evidence is needed to prove the therapeutic efficacy and safety of MSNs, there is still a long way to go to fully realize MSN systems containing drugs in the clinical market.


We piloted a community-based intervention to improve outcomes among adolescents living with HIV who were transitioning to adult-oriented care in Lima, Peru. We assessed feasibility and potential effectiveness, including within-person changes in self-reported adherence, psychosocial metrics (NIH Toolbox), and transition readiness . From October 2019 to January 2020, we enrolled 30 adolescents (15–21 years). The nine-month intervention consisted of logistical, adherence and social support delivered by entry-level health workers and group sessions to improve health-related knowledge and skills and social support. In transition readiness, we observed within-person improvements relative to baseline. We also observed strong evidence of improvements in adherence, social support, self-efficacy, and stress, which were generally sustained three months post-intervention. All participants remained in treatment after 12 months. The intervention was feasible and potentially effective for bridging the transition to adult HIV care. A large-scale evaluation, including biological endpoints, is warranted.The online version contains supplementary material available at 10.1007/s10461-022-03725-2. Expanded access to antiretroviral therapy (ART) has led to major improvements in the survival of children who acquire HIV early in life. This means that providers and programs are faced with the challenge of caring for a group of patients living with HIV that is also dealing with the many developmental, emotional and behavioral issues of adolescence. These include the desire for peer acceptance, vulnerability to mental health and substance use disorders, and the potential consequences of early sexual debut  –6. And, For many ALWH, the transition to adult HIV care is a tumultuous time, marked by episodic care and declines in HIV viral load suppression and CD4 cell counts , 20. ThiAlongside an urgent need to identify effective transition interventions is a growing recognition of the need for interventions that are tailored to local context and to specific subgroups. A recent review on care transition studies for ALWH identified an absence of studies from Latin America and the Caribbean, where the experiences of ALWH likely differ from those in high-income or high prevalence settings . There iIn Peru, there are an estimated 91,000 people living with HIV, with the highest concentration in the capital, Lima . While pART was made available free-of-charge through the public sector in 2004 and remains largely centralized with most patients receiving treatment through public sector hospitals. Care under Peru’s National HIV Program is provided by a multidisciplinary team of providers including physicians, nurses, psychologists, and peer-supporters. ART is typically dispensed monthly, but may be dispensed at longer intervals for patients who have established consistent adherence.For adolescents that acquired HIV in early childhood, the transition from a pediatric to an adult HIV clinic often occurs at age 18, though it may occur as young as 15 for adolescents transitioning within the same health facility. Older, newly-diagnosed adolescents may transition directly into adult HIV care, bypassing the pediatric clinic. Pregnancy during adolescence is common with 17% of 20- to 24-year-old women giving birth before age 18 . If an aWhile, we know of no published studies examining health outcomes among ALWH following transition to adult care in Peru, studies suggest that adherence, CD4 cell count, and viral suppression decrease throughout adolescence , with laWe included ALWH aged 15 to 21 years who were on or newly initiating ART, enrolled in HIV care at a participating public sector clinic, and scheduled to transition to adult HIV care, either due to a recent HIV diagnosis or because they had aged out of their pediatric clinic. We consecutively enrolled patients representing the three common transition experiences in this setting, aiming for approximately ten participants per group: adolescents transitioning from a pediatric clinic to an adult clinic at a new facility; adolescents transitioning from a pediatric to an adult clinic within the same facility; and adolescents newly initiating treatment in an adult facility. ALWH who were previously lost from care during transition but interested in re-engaging in treatment were also eligible to participate. Adolescents were excluded if they lived outside of metropolitan Lima. Enrollment took place from October 2019 to January 2020 at three public sector hospitals (one pediatric facility and two facilities with distinct on-site pediatric and adult clinics). Ministry of Health clinical collaborators consecutively referred eligible participants to study staff. A Youth Advisory Board comprising a diverse group of young people living with HIV provided feedback on all aspects of the study. Adolescents who had previously withdrawn from care were referred by their clinicians or Youth Advisory Board members and contacted by study staff.The intervention was nicknamed “PASEO” (meaning ‘crossing’ or ‘passage’ in Spanish) after its core elements: peer engagement, accompaniment, support and education. In short, PASEO aimed to provide in-person accompaniment to ALWH throughout the transition process through the provision of individualized support, including adherence support, to address barriers to care and treatment  by providing medical, material, and social support delivered by compensated entry-level or lay health workers who liaise with formal health services .PASEO also aimed to foster health-related skills, knowledge, and psychosocial well-being needed to thrive in the adult clinic and more broadly. Intervention activities were delivered in two phases, an intensive phase and a taper phase . The intensive phase began just prior to transition  and ended after six months. A three-month taper phase, during which the intensity of study activities was reduced, followed the intensive phase. Below, we describe each intervention component in detail as well as adaptations made to accommodate stay-at-home orders invoked on March 15, 2020, due to the SARS-CoV-2 pandemic. Participants had received between 1.4 and 5.3 months of in-person intervention (median: 3.1 ) when in-person activities were suspended and programming was implemented virtually. Adolescents were provided phone credit to enable participation in virtual programming.Health system navigation and clinic accompaniment. To facilitate the transition to care in the adult clinic, trained health promoters  employed by the nongovernmental organization Socios En Salud accompanied adolescents to their first appointments; facilitated enrollment in public health insurance and completion of other administrative requisites; helped troubleshoot logistical and/or social challenges ; and served as a liaison between the patient and pediatric and adult clinical providers. Clinic visit transportation was provided based on economic need, as determined by the study social worker. All but one participant had attended at least one accompanied in-person clinic visit prior to SARS-CoV-2 stay-at-home orders. The exception was an individual who was scheduled to re-initiate care in mid-March 2020. While hospital guidelines precluded in-person accompaniment for this participant, intervention staff coordinated with HIV program staff to ensure that adolescent would be seen in the clinic. Study staff coordinated private telehealth appointments for adolescents requiring clinical consultation during stay-at-home orders.Routine check-in visits. Health promoters visited the participant’s home or another mutually-agreed upon location at least monthly to review ART adherence, identify barriers to care and adherence, remind patients of upcoming medical encounters, screen for and follow-up on clinical and social problems and offer social support. The frequency of check-ins was individualized and commensurate with the level of support needed. Visits tended to occur more frequently for participants lacking family support, re-initiating ART or with a history of unstable adherence.Directly Observed Treatment (DOT). Home-based DOT was offered to adolescents identified as at risk of non-adherence . ALWH newly initiating ART chose whether they wished to receive DOT. Eligible ALWH who opted into DOT were assigned to a Ministry of Health community health worker from the same neighborhood to observe ART ingestion daily, ensure treatment was taken as prescribed and offer social support. Following invocation of stay-at-home orders, DOT was conducted virtually by Socios En Salud health promotors via telephone, video or short message service, depending on participant preference. Some participants elected to participate in group video DOT, creating an additional opportunity to build social support.Social support groups, health education sessions and skill-building workshops. Social support groups took place at least once monthly (10 adolescents per group). The two-hour sessions were facilitated by a Peruvian study psychologist and one peer youth living with HIV. Based on timing of enrollment, adolescents were eligible to have attended between two and five in-person sessions prior to stay-at-home orders. Conducting these sessions online was largely unsuccessful: many adolescents felt they lacked privacy at home to discuss personal topics [l topics , and othHealth education sessions and skill-building workshops were conducted on topics such as HIV, substance use, sexual health, self-esteem, nutrition, and gender and sexual identity. In-person sessions took place at least once monthly , while virtual sessions took place one to three times weekly . For virtual sessions, participants could join live, allowing interaction with the speaker and other participants via chat, or view a recording.Mental health screening, referral and support. Participants were evaluated for depressive symptoms using the Patient Health Questionnaire-9 (PHQ-9), a tool previously validated in Spanish [ Spanish , and wid Spanish . Adolesc Spanish  and refe Spanish .Data collection took place from October 2019 to January 2021 and included indicators of intervention feasibility and potential effectiveness, and social, clinical, and demographic factors that could challenge transition.Feasibility indicators aligned with selected dimensions of acceptability and demand . AcceptaPreliminary evidence of effectiveness is an impact indicator examining whether a new intervention shows promise of success with the intended population. We generated preliminary evidence of effectiveness by calculating changes in transition readiness at 9-months, relative to baseline, and in self-reported adherence, perceived instrumental and emotional support, self-efficacy and stress at 6, 9, and 12-months, relative to baseline. Follow-up measurements corresponded to the end of the intensive phase, the end of the taper phase, and three months after intervention, respectively.Baseline clinical data, including CD4 cell count and viral load, were recorded from clinical charts. Follow-up measurements were rarely available due to testing disruptions resulting from the SARS-CoV-2 pandemic.Instruments. Participants self-administered surveys in Spanish on a tablet device. We assessed self-reported adherence during the prior 30-day period with three questions: “How many days did you miss at least one dose of any of your ART medications?”; “How often did you take your ART medications correctly?” ; “How well would you say you took your HIV medications, as directed by your doctor?” . We assessed perceived instrumental support, emotional support, perceived stress, and self-efficacy using the Spanish fixed-form version of the NIH Toolbox Emotion Battery (version 2.0) for ages 18–85. All have a 5-point ordinal scale ranging from “never” to “always”, with higher scores indicating higher levels [r levels , 51. We r levels  consistsr levels . The queFeasibility indicators were reported as descriptive statistics. To examine changes in outcomes during the different phases of intervention implementation, we calculated frequencies, medians, and interquartiles ranges across time-points and calculated within-person change from baseline to each of the three follow-up points and tested whether this quantity differed from zero, using paired t-tests or Wilcoxon signed rank tests, as appropriate. For the NIH toolbox measurements, we report raw scores instead of the t-values validated in a U.S. population. To understand whether potential effectiveness differed among subgroups, we stratified analyses by early childhood versus recent diagnosis and whether the adolescent had been lost from care or had a history of chronic non-adherence. Data were analyzed using SAS version 9.4 .The authors declare no conflicts of interest. Ethical approval was granted in Peru by the Institutional Research Ethics Committees of the Instituto Nacional de Salud del Niño, Hospital Nacional Arzobispo Loayza, and Hospital Nacional Hipólito Unanue. In addition, ethical approval was granted by the Institutional Review Board (IRB) of Harvard Medical School in the USA. Written informed consent was obtained from adolescents 18 years of age and over or from guardian(s) of adolescents < 18 years. Participants < 18 years provided informed assent. Three adolescents < 18 years without a guardian provided assent and were granted a waiver of consent.≥ 4). Median emotional and instrumental support scores fell at the midpoint of the range of possible values while median self-efficacy and perceived stress fell below the midpoint of the range of possible values and median transition readiness fell at or above the midpoint of possible values . There were 41 virtual sessions offered, and 28 adolescents (93%) participated in at least one of these sessions .Of 36 adolescents referred for participation, six refused to participate (16.7%). Four were adolescents who had previously withdrawn from HIV care and did not wish to reengage. Two opted out because of scheduling conflicts with study activities. Once enrolled, no participant withdrew from the nine-month intervention, 12-month research study, or ART (12 months of follow-up). Of the 30 adolescents, all but three (90%) attended at least one in-person social support session. Based on timing of enrollment, 10 participants were eligible to have participated in five in-person social support sessions and 20 participants were eligible to have participated in three sessions. The median number of sessions attended by those participating in Changes in adherence, psychosocial scale scores, and transition readiness scores are shown in Table We provide quantitative evidence supporting the feasibility and potential effectiveness of a community-based intervention designed to improve health outcomes for ALWH in Lima, Peru. The adolescents in this cohort were diverse in terms of their medical needs and social circumstances, which included depression, housing instability, poverty, lack of parental support, pregnancy and living in a foreign country. A key strength of the intervention was its comprehensive nature  and individualized design . Research has highlighted the limited efficacy of a “one size fits all” approach for community-based interventions , 57, 58,We found the PASEO intervention to be highly feasible based on metrics of acceptability and demand. There was a low refusal rate for enrollment, no participants were lost to follow up, and adolescents demonstrated high-attendance in group sessions. The potential effectiveness of PASEO is supported by within-person improvements in adherence, psychosocial indicators, and transition readiness; this improvement was often sustained three months after the intervention’s intensive phase. Importantly, these improvements appear to hold up across subgroups of adolescents characterized by timing of diagnosis (early childhood infection versus recent diagnosis) and among those with a history of non-adherence. This suggests that the lay health workers were effective at individualizing support to adequately meet the needs of each adolescent. Importantly, these data also corroborate that PASEO aligns with World Health Organization criteria for adolescent-friendly care in that it was acceptable (adolescents were willing to engage), equitable , appropriate (offering the right menu of services) and effective  . To furtA number of intervention studies addressing the transition period are underway in low-or-middle-income and high-burden settings , 62. WhiThis pilot study was underway when the SARS-CoV-2 pandemic emerged, during which stay-at-home orders were intermittently instated. These circumstances required us to adapt the intervention to a virtual format; however, improvements in key metrics suggest that the pillars of the intervention  were preserved under this hybrid model. The lack of a control group precludes definitively concluding that the intervention caused these improvements; however, baseline measurements preceded SARS-CoV-2, while follow-up measurements occurred in the first six months of the pandemic; therefore, the expected time trend in these outcomes would likely have attenuated any PASEO-related improvements . While uIn conclusion, the PASEO intervention was feasible and demonstrated promise for improving myriad self-reported health outcomes in a diverse cohort of ALWH. Future studies should include a large-scale impact evaluation including biological outcomes and assessment of long-term effectiveness beyond the life of the intervention.Additional file 1: Electronic Supplementary Materials.Information on file format. Key components of intervention, overview of intervention implementation, adaptation of the “Am I on TRAC” transition readiness questionnaire, analyses of effectiveness outcomes, stratified by early childhood versus recent diagnosis and whether the adolescent had been lost from care or had a history of chronic non-adherence.Below is the link to the electronic supplementary material.Supplementary Material 1


Over the past couple of decades, many telecommunication industries have passed through the different facets of the digital revolution by integrating artificial intelligence (AI) techniques into the way they run and define their processes. Relevant data acquisition, analysis, harnessing, and mining are now fully considered vital drivers for business growth in these industries. Machine learning, a subset of artificial intelligence (AI), can assist, particularly in learning patterns in big data chunks, intelligent extrapolative extraction of data and automatic decision-making in predictive learning. Firstly, in this paper, a detailed performance benchmarking of adaptive learning capacities of different key machine-learning-based regression models is provided for extrapolative analysis of throughput data acquired at the different user communication distances to the gNodeB transmitter in 5G new radio networks. Secondly, a random forest (RF)-based machine learning model combined with a least-squares boosting algorithm and Bayesian hyperparameter tuning method for further extrapolative analysis of the acquired throughput data is proposed. The proposed model is herein referred to as the RF-LS-BPT method. While the least-squares boosting algorithm is engaged to turn the possible RF weak learners to form stronger ones, resulting in a single strong prediction model, the Bayesian hyperparameter tuning automatically determines the best RF hyperparameter values, thereby enabling the proposed RF-LS-BPT model to obtain desired optimal prediction performance. The application of the proposed RF-LS-BPT method showed superior prediction accuracy over the ordinary random forest model and six other machine-learning-based regression models on the acquired throughput data. The coefficient of determination (Rsq) and mean absolute error (MAE) values obtained for the throughput prediction at different user locations using the proposed RF-LS-BPT method range from 0.9800 to 0.9999 and 0.42 to 4.24, respectively. The standard RF models attained 0.9644 to 0.9944 Rsq and 5.47 to 12.56 MAE values. The improved throughput prediction accuracy of the proposed RF-LS-BPT method demonstrates the significance of hyperparameter tuning/optimization in developing precise and reliable machine-learning-based regression models. The projected model would find valuable applications in throughput estimation and modeling in 5G and beyond 5G wireless communication systems. Effective data processing and analysis have become a huge task due to the upsurge in massive data collection from various wireless communication devices and cellular networks . MassiveIn recent decades, machine-learning-based regression models have emerged as vital models in carrying out prognostic modeling and analysis of relevant datasets in all fields of physical sciences, medical science, and engineering domains ,13,14,15Several machine learning techniques have been explored ,19,20,21Many attempts have been made to handle RF hyperparameter tuning problems in the literature to boost its predictive application performance. In the literature ,7, the aIn view of the preceding literature, there is no existing work that reports a machine-learning-based boosted regression ensemble combined with hyperparameter tuning for optimal adaptive learning. To this end, this paper proposes a random forest machine-learning-based model combined with a least-squares boosting algorithm and Bayesian hyperparameter tuning to boost its predictive application performance. The proposed regression model is termed the RF-LS-BPT model. A detailed application of the proposed RF-LS-BPT model to real-time throughput data acquired at different user equipment terminal locations in 5G mobile broadband cellular networks was investigated. Our proposed RF-LS-BPT model offers a new hybridized predictive modeling method to help network operators and engineers regularly conduct improved extrapolative analysis of different cellular network data for planning and management purposes.We first give a detailed statistical analysis of the acquired throughput data through performance status reporting at the different user equipment terminal locations with respect to the tested communication distances from the transmitter.We provide performance benchmarking of adaptive learning capacities of different key machine-learning-based regression models with the choice regression model, which is the random forest.We propose an RF-LS-BPT regression model for improved dataset predictive modeling and learning.The proposed RF-LS-BPT regression model was applied in detailed, accurate throughput data modeling and learning using different performance indicators.The foremost contributions of this research paper are highlighted as follows:The remaining part of this paper is structured into four sections as follows. First, the general concept of random forest is described, and the exploratory data analysis (EDA) method applied is highlighted in this section. The mathematical description of the RF regression model and least-squares boosting (LS-Boost) is also broached.The RF is an ensemble of decision-tree-based machine learning methods. It was proposed in  by BreimGenerally, many factors impact on predictive modeling capacities of machine-learning-based models and methods, especially the surrogate types such as the RF, SVM, DT, GPR, and NN. These include the learning rate, tree number, training algorithm, and hyperparameter tuning algorithm. In , the autIn this study, an integrated exploratory approach was taken to examine some of the aforementioned factors in RF predictive modeling performance capacity. Our exploratory approach considers the integration of a random forest (RF)-based machine learning model combined with a least-squares boosting algorithm and Bayesian hyperparameter tuning method for real-time extrapolative data analysis.The exploratory data analysis (EDA) method  was utilIn broad mathematical terms, an RF is a special predictor whose main constituents are built on randomized tree ensembles A, the RF estimate can be expressed as (1):For a finite tree number, M is sufficiently large), the RF estimate turns to (2):For an infinite tree number :Consider a data training sample Owing to the hypothetical bias and variance issues, the fitted model and the resulting predicted outcome may severely suffer from underfitting or overfitting problems, leading to a high error between the targeted response and the estimated variables. In order to address such drawbacks, the inconsistency of  learner ,38. At eThis section presents detailed information on the entire procedure engaged to achieve the research aim. Particularly, the method of 5G throughput data collection, the proposed RF-LS-BPT implementation algorithm, and its implementation process are provided in this section.The current study utilized field measurements taken in diverse urban environments in the United States to test and validate the proposed learning-based models. The field measurements were taken to assess the commercial 5G performance on smartphones and made available online . The 5G Additionally, the performance of the app in terms of web browsing, HTTP download, and volumetric video streaming over 5G was critically examined. The experiments, which consume over 15 Tb data, were carried out over T-Mobile, Sprint, and Verizon 5G networks. Verizon offers operational mm-wave-based 5G services to subscribers in the investigated environments where dense 5G base stations are deployed. T-Mobile employs mm-wave, while Sprint uses a mid-band frequency at 2.5 GHz. In the field measurements, the authors captured about 6.8 million data points obtained from the 5G coverage in downtown Minneapolis, USA .Two types of commercially available off-the-shelf (COTS) 5G-capable smartphones were used in the experiments. These were the Motorola Moto Z3 and Samsung Galaxy S10 5G (SM-G977U). For brevity, these are described as MZ3 and SGS10, respectively. The SGS10 uses an in-built 5G radio, while the MZ3 uses an external 5G mod to access 5G networks. The mobile device used is the SGS10, and it is 4G- and 5G-compatible, allowing comparison on the same device. Four locations were considered for the experiments carried out on Verizon’s network . TypicalLoad the throughput datasets into MATLAB.Examine the datasets to obtain relevant insights.Presence of correlated features.Missing values and outliers.Preprocess the datasets to cater for the identified missing values and outliers.Transform the datasets RF-LS-BPT modeling format.Split the datasets into two, with 0.3 portions for testing and 0.7 portions for training.Engage the default RF ensemble fitting tool in MATLAB for the data training and testing.Evaluate the default RF ensemble fitting through data training and testing.Choose an appropriate RF aggregation technique. LS-Boost was chosen here.Identify the most relevant RF hyperparameters.Determine optimal values of the RF hyperparameters using the optimization option I MATLAB , which is based on the Bayesian optimization process.Optimize the RF Regression ensemble results using the cross-validation process.Build the final RF-LS-BPT model combing the LS-Boost algorithm with tuned optimal RF hyperparameter values.Engage the resultant RF-LS-BPT model on the entire throughput quality datasets.Test the resultant RF-LS-BPT using a 0.3 portion of the data and new data.Assess and report the predictive performance of the resulting RF-LS-BPT model.The entire RF-LS-BPT process, which is revealed using the flowchart in Algorithm 1: Also, The RF Regression with least-squares boost (LS-Boost) is given in Algorithm 1.Input:Training set:Learning rate value, v and Tree number, A, obtained through Bayesopt,Loss function, Output:Regression mode, Training Process:EndThe mean absolute error (MAE)  given in® Core™ i3-10110U and Intel® Turbo Boost Technology, 4 MB L3 cache, 2 cores was used. First, in this section, we start by revealing the status of the acquired 5G throughput qualities attained at close communication distances of 25, 50, 75, 100, and 160 m between the transmitter and UET. This is followed by results and discussion on the throughput data training and testing accuracy achieved using seven machine learning models with their default parameters. Also contained in this section are throughput data training and testing results achieved using the proposed RF-LS-BPT model versus the standard RF modeling approach, plus results on throughput data training and testing using LS-boosting and bagging.Detailed results and discussion are contained in this section. All computations, coding, implementation, and graphics were conducted using MATLAB software environment with the aid of an HP laptop (Elitebook) with an IntelThe throughput quality remains an exclusive higher-layer performance indicator for assessing data transmission quality and integrity in mobile broadband networks. Remarkably, the actual throughput quality at the UET can be influenced by critical factors such as user location and communication distance from the transmitter. The user data throughput expresses the speed at which a user can reliably send data and receive the same at the user equipment terminal (UET). It also expresses the quantity of data in bits per second (bps) conveyed and delivered over the cellular network within a specific period. The graphs in Throughput quality status in terms of maximum, minimum, and mean throughput quality values attained at the various distances are summarized in In addition to hyperparameters, machine learning models have their default parameters internally built for specific tasks. While the default parameters are inevitably used to learn, hyperparameters are objectively set by the user to guide the learning process optimally. Here, five key machine learning models with default parameter regression settings were first engaged for throughput data training and testing. The machine learning models are the multi-layer perceptron neural network (MLP-NN), random forest (RF), support vector machine (SVM), K-nearest neighbor (KNN) model, Gaussian process regression (GPR), and decision tree (DT). The generalized least-squares (GLS) model was also employed in the regression process. The main aim of using other machine learning methods is also to assess their adaptive learning capability with the choice of RF method. Shown in Although the RF-based regression model outperforms other selected machine learning models, which used benchmarks, as shown above, some hyperparameters can be tuned to further optimize it for improved performance during predictive data modeling and learning. Furthermore, the large prediction error attained by the standard RF-based regression model can be attributed to the high divergence between the input variables and targeted response. As mentioned earlier, the target error response can be reduced using the LS-Boosting technique, hence the proposed RF-LS-BPT model. In order to prevent overfitting or underfitting, the hyperparameters were tuned to minimize the prediction error further . In ordeDue to hypothetical bias and variance issues, the predicting model or the targeted response may severely suffer from underfitting or overfitting problems, leading to high error between the targeted response and the estimated variables. In order to address such drawbacks, the prediction model needs to be placed under control by employing the bagging (Bag) or least-squares boosting (LS-Boost) algorithm. While bagging employs a simple technique of result averaging to aid a model in achieving its desired prediction, boosting utilizes a weighted mean of results in aiding a model in actualizing its prediction method. In the LS-Boost algorithm, hundreds or more weak learners (trees) are engaged for training, and the error is iteratively updated to improve learning. Here, the robust performance of the adopted LS-Boost algorithm in the proposed RF-LS-BPT model compared to the bagging algorithm in training and testing to learn the throughput data obtained at collection points is provided in The throughput quality remained an exclusive higher-layer performance indicator for assessing data transmission quality and integrity in mobile broadband networks. The user data throughput expresses the speed at which a user can reliably send data and receive the same at the user equipment terminal (UET). Generally, the amount and quality of throughput at the UET can fluctuate significantly, subject to many influencing factors. However, many factors can influence user data throughput quality. The key ones include network propagation environment, user location, communication distance, the disproportion between upload and download rates, available channel bandwidth, network traffic load, propagation channel conditions, signal quality, signal coverage, and modulation/coding scheme. The first objective of this research was to determine the actual throughput quality attained at the UET at a close communication distance of 25, 50, 75, 100, and 160 m from the transmitter over a typical 5G mobile broadband cellular network. The second objective was to appraise the popular machine learning predictive modeling techniques in the literature and optimize the best one using a robust approach for optimal adaptive prediction modeling and learning of the acquired stochastic throughput quality. By following the two main objectives, the aims of the proposed learning-based models were achieved. Apart from examining the impact of transmitter–receiver communication distances on throughput quality status as in this study, there is also a need to conduct a detailed empirical investigation of the influence of variables on throughput quality. This need, however, is slated for our future research. In addition, future work would investigate the predictive capability of deep neural network models such as long short-term memory and other evolutionary-based regression techniques such as particle swarm optimization and genetic algorithms.


Background: Hand hygiene is essential to preventing the spread of disease in hospitals. Renewed emphasis has been placed on hand hygiene during the COVID-19 pandemic. We investigated whether UNC Medical Center’s well-established Clean-In Clean-Out (CICO) program for hand hygiene observations was sustainable throughout a public health and healthcare crisis and whether the COVID-19 pandemic had an effect on hand hygiene compliance. Methods: UNC Medical Center utilizes a crowd-sourced hand-hygiene audit application, CICO, to track hand-hygiene observations, compliance, and feedback. This application encourages participation from all staff and promotes providing real-time feedback in the form of a compliment or reminder when performing hand hygiene observations. During this evaluation, hand hygiene data were queried from the CICO application on the number of observations performed, hand hygiene compliance percentage, and feedback compliance percentage from July 2019 to December 2020. Hand hygiene data were compared to patient volumes in different care settings and the number of hospitalized patients being treated for COVID-19. Results: Initial increases in hand hygiene observations, compliance, and feedback were detected in the months leading up to UNC Medical Center receiving its first SARS-CoV-2–positive patient. Observations were highest when patient volumes were low due to closed clinics and restrictions on elective surgeries (Figure Conclusions: Despite the additional strain on healthcare staff during COVID-19, the CICO model was a sustainable method to track hand hygiene observations and compliance. Notably, however, engagement was highest when patient census was lower, demonstrating that operating at a high capacity is not beneficial for patient safety. Due to the success and sustainment of the CICO program, UNC Medical Center used this model to create a Mask-On Mask-Up campaign to engage staff to submit observations, track compliance, and encourage feedback to promote the appropriate use of masks during COVID-19.Funding: NoDisclosures: None


Intra-articular injection is indicated for mild or moderate osteoarthritis (OA). However, the superiority of cell-based injection and the role of diverse cell sources are still unclear. This study aimed to compare the therapeutic effect of intra-articular injection with mesenchymal stem cells (MSCs) and cell-free methods for OA treatment.A literature search of published scientific data was carried out from PubMed, MEDLINE, Embase, Cochrane Library, Web of Science, and China National Knowledge Internet (CNKI). Randomized controlled trials (RCTs) compared the efficacy and safety of MSC and cell-free intra-articular injection treatments for OA with at least 6-month follow-up.Dual network meta-analysis validated the therapeutic advantages of MSC treatments  but also suggested a potential negative safety induced by cell injection . For the MSC source aspect, adipose mesenchymal stem cells (ADMSCs) and umbilical cord mesenchymal stem cells (UBMSCs) showed a better curative effect on pain relief and function improvement compared with bone marrow mesenchymal stem cells (BMMSCs).Intra-articular injection of MSCs is associated with more effective pain alleviation and function improvement than cell-free OA treatment. However, the potential complications induced by MSCs should be emphasized. A comparative analysis of the MSC sources showed that ADMSCs and UBMSCs exerted a better anti-arthritic efficacy than BMMSCs.Schematic illustration of MSC-based intra-articular injection for treating OA. Three major MSCs  are extracted and expanded in vitro. Subsequently, the amplified MSCs are concentrated and injected into the knee joint to treat OA.The online version contains supplementary material available at 10.1186/s13075-022-02953-0. Intra-articular injection of MSCs shows better improvements in pain and function than cell-free OA.MSC-based therapy is associated with neglected treatment-related adverse event risk.For the selection aspect, ADMSCs or UBMSCs may exert a better anti-arthritic efficacy than BMMSCs.Osteoarthritis (OA) is a degenerative disorder of common joints such as the knee, hip, shoulder, and ankle. With a rising aging population, OA has led to immeasurable health and financial burden because it mainly affects elderly people . SeveralRecently, in-depth research on regenerative medicine represented by mesenchymal stem cells (MSCs) has provided a novel therapeutic strategy for OA treatment . MSC-basThis article reviewed the latest published research reports related to these therapies of OA. We focused on the comparison of efficacy and safety of cell-based and cell-free intra-articular injection therapies. A dual network meta-analysis based on Bayesian and SUCRA models was also performed to provide a more reliable reference for clinical injected therapy of OA. The latest research progress related to these therapies, the mechanism of function, and the adverse effects of them were summarized and concluded. According to the results, the application prospect of intra-articular injection was analyzed in the treatment of osteoarthritis.This study followed the preferred reporting items (PRI) for the systematic reviews and incorporated Network Meta-Analysis (PRISMA-NMA) for meta-analyses Additional File The inclusion criteria for enrollment of studies into network meta-analysis were participants 18 and above years of age; participants with unilateral or bilateral symptomatic knee OA (as described by the American College of Rheumatology criteria); visual analog scale (VAS); and Kellgren-Lawrence grade; participants who received an intervention of a single intra-articular injection with MSCs  and received a single intra-articular administration of PRP, HA, saline, or conservative treatment ; and efficacy parameters including VAS scores, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index of the total, and safety indicators such as the incidence of adverse events and the study design of randomized controlled trials (RCTs) with a follow-up of at least 6 months. The exclusion criteria included non-RCT, case reports, conferences, comments, animal experiments, reviews, non-comparable studies, and studies with insufficient variables or a small sample size (included less than ten participants) , Cochrane Library, Embase, MEDLINE, PubMed, and Web of Science were utilized to conduct a literature search based on the following algorithm: (“osteoarthritis” or “knee osteoarthritis” or “knee pain”) or  and randomized controlled trials. The reference lists of the obtained relevant review or studies were searched to prevent undiscovered omissions. The retrieval process was conducted from the date of inception to January 2021, and the language used was strictly English and Chinese.The extracted data included the authors, country, publication date, sample size, mean age, sex distribution, intervention details, outcome parameters, and follow-up time. The data were independently extracted by two authors (YZ and FH) and checked by a third reviewer (XZ). For efficacy index, VAS scores and WOMAC index of total, function, pain, or stiffness were collected pre- and post-intervention between the two arms. The incidence of adverse events  for the two groups was recorded after the intervention.The Cochrane Collaboration Tool was used by the two independent reviewers (YZ and FH) to assess the methodological quality of each study enrolled for the analysis. According to this tool, “low,” “unclear,” or “high” risk were assigned to selection bias, detection bias, attribution bias, performance bias, reporting bias, and other biases.I2 value reflected a possible heterogeneity of the parameters. The global or local consistency was evaluated using an inconsistency model or node-splitting method, respectively, to determine the closed-loop parameters [The Review Manager (v 5.3), STATA v 14.0), WinBUGS (v 1.4), and R (v 3.6) software were utilized to perform data analyses following a prescribed order in this study. First, a conventional pairwise meta-analysis was conducted using random effects model with the STATA software (v 14.0). This estimated the relative risk (RR) for the dichotomous variables . The data from the continuous variables have a 95% credible interval. Second, network meta-analysis was performed based on a Bayesian random effects model using the GeMTC R package. The Markov chain Monte Carlo (MCMC) method was applied to obtain the pooled ranking probabilities. This was performed through 100,000 iterations for each three MCMC chains with a burn-in period of the initial 50,000 iterations. Third, to calibrate the reliability of the ranking probabilities, a SUCRA model  was gene.0, WinBUrameters .A total of 1756 articles were identified and extracted from the different databases and literature sources. Out of the 1756 extracted articles, 1283 articles were included after the elimination of the duplicates. The 1283 studies remained for the title and abstract screening. Subsequently, the full-text review of 138 studies was conducted. Out of the 138 studies, 122 of studies were excluded according to the exclusion criteria. Finally, 16 RCTs with 612 patients were enrolled in this network meta-analysis  than cell-free treatments .The intra-articular injection of MSCs showed better function improvement in WOMAC index totals than the cell-free treatments , WOMAC function , and WOMAC pain .Based on a pairwise meta-analysis, it was reported that the MSC intra-articular treatments showed a rate of incidence of adverse events but were not significantly different from the rate of incidence in cell-free injection treatments  and cell-free treatments  Fig. A. The inTherefore, according to the Bayesian model, the VAS ranking of the treatments was ADMSC, BMMSC, PRP, UBMSC, saline, HA, and CT Fig. A. AccordA total of 10 RCTs that comprised 368 patients reported the WOMAC total between intra-articular injections of MSCs  and cell-free treatments  Fig. B. The raA total of 8 RCTs that comprised 244 patients reported the WOMAC function between MSC treatments  and cell-free treatments  Fig. C. Any twA total of 6 RCTs that composed of 202 patients reported the WOMAC pain in the intra-articular injection with MSC treatments  and cell-free treatments  Fig. D. Intra-A total of 6 RCTs that comprised 202 patients reported the WOMAC stiffness between MSC treatments  and cell-free treatments  Fig. E. There A total of 16 RCTs that comprised 612 patients reported adverse events in MSCs  and cell-free treatments  Fig. F. There The loop test was performed on the closed-loop parameters  to determine the underlying heterogeneity of the above outcomes. It was found that the loop-specific heterogeneity of each loop was less than 5%. This suggests a negligible heterogeneity in our results Fig. S. Both thAlthough surgical therapies such as arthroplasty and osteotomy relieve pain and enhance mobility in osteoarthritis patients, several complications and cost of the interventions limit their application in early and moderate OA patients . On the To overcome these challenges, this study built a comparable network model among BMMSC, ADMSC, UBMSC, PRP, HA, saline, and CT based on a Bayesian random effects model. The model was calibrated according to SUCRA to draw a reliable conclusion. Our results of this study show that intra-articular injections of MSCs are a better pain reliever than cell-free treatment. A parallel tendency was also observed in the functional recovery. The agminated MSCs in the articular cavity of a patient cause a lubricating action and can also release bioactive factors, e.g., transforming growth factor-β, collagen type II, and sulfated glycosaminoglycans. This help regulate the balance between anabolism and catabolism by targeting cartilage, synovium, and subchondral bone . Based oAccording to our pairwise analyzed results, the cell-based therapy did not increase the risk of adverse events as compared with cell-free treatments. For the network analysis aspect, conservative treatment was associated with an optimum security since no puncture procedure was implemented. Intriguingly, the safety rank of PRP and saline was superior to BMMSCs, ADMSCs, and UBMSCs. This suggests that injected MSCs may result in a higher hazard risk. In combination with pairwise and network results, we considered that enough attention should be paid to MSC treatments in the clinic, though most of the adverse events observed are mild and self-alleviate local reactions without the need for specific intervention. Freitag et al. reported that two patients received a short period of oral prednisolone to treat prolonged effusion after ADMSC injection . Lamo-EsThe choice of MSC sources is another crucial concern for cell-based therapy. It was theoretically considered that MSCs exerted a similar therapeutic effect due to their inherent multiple differentiation potency. However, clinical trials showed a discrepant outcome in terms of different MSC types. Wei et al. compared the efficacy of MSCs from different sources and suggested that ADMSCs were the best choice for relieving pain whereas UBMSCs were the most effective method for improving function . AccordiSeveral limitations of this study should be noted. First, the study compared three MSC sources with cell-free treatments, but another preclinical method with insufficient data, e.g., synovial mesenchymal stem cells (SMSCs), was not analyzed. Second, additional assessments such as KOOS, Lysholm Knee Scale (Lysholm), and Whole-Organ Magnetic Resonance Imaging Score (WORMS) need to be considered in the future based on more RCTs. Third, due to the relatively short follow-up time, the long-term clinical outcomes of MSC treatments are unclear. Fourth, the follow-up period of enrolled studies was not completely consistent, which may introduce another potential selection bias. We will continue to focus on the therapeutic effects of MSC treatments on OA based on a long-observed period.This research analyzed the advantages and limitations of intra-articular injection of three MSCs  for OA patients using a dual network meta-analysis. Our results show that intra-articular administration of MSCs has better pain relief and function improvement than cell-free therapy for treating OA. Furthermore, the study reveals that ADMSCs and UBMSCs are superior to BMMSCs as the MSC sources for OA treatment. However, MSC-based therapy may cause some potential adverse events that need to be paid enough attention to. More studies with large sample sizes and long-term follow-up are required to make conclusive claims in the future.Additional file 1: Fig. S1. Ranking probability based on SUCRA model. Different area under curve represents the predicted rank for each intervention (From first to seventh). (A) VAS score; (B) WOMAC Total; (C) WOMAC Function; (D) WOMAC Pain; (E) WOMAC Stiffness; (F) Adverse events. SUCRA, surface under the cumulative ranking curve. Fig. S2. Heterogeneity assessment according to the loop test. (A) VAS score; (B) WOMAC Pain; (C) Adverse events. Fig. S3. Inconsistency assessment according to the inconsistency model. (A) VAS score; (B) WOMAC Pain and (C) Adverse events.Additional file 2. PRISMA 2020 Checklist.Additional file 3: Table S1. Pairwise meta-analysis for each outcome based on random effects model. Table S2. Local consistency test based on node-splitting method for closed-loop variables. Table S3. Consistency test for closed and open-loop data based on the comparison of different model variances.