Community-engaged learning is used in Master of Public Health programs toenhance student training, connect with communities, help solve societalissues, develop competencies, and build partnerships. However, it is unclearhow much community-engaged learning components supplement existing Master ofPublic Health programs and prepare students in developing thesecompetencies. Thus, the aim of this study was to apply an explanatorymixed-methods study design to evaluate a Canadian Master of Public Healthprogram’s community-engaged learning activities and propose recommendationsto strengthen public health training and course delivery.n = 25), focus group discussion with a subset of thesestudents (n = 7), and one-on-one semi-structured telephoneinterviews with community partners who had previously hosted Master ofPublic Health students for practicum placements(n = 11).We conducted a questionnaire among Master of Public Health students(Community-engagement enhanced learning among Master of Public Healthstudents, with the practicum placement, and program development capstoneresulting in the largest self-reported development. Students in the focusgroup indicated community engagement provided skill and professionaldevelopment, but also identified wanting additional curriculum coverage onvarious statistical software and qualitative research methods. Interviewswith community partners revealed benefits of practicum placements such asmutual knowledge transfer, increased organizational capacity, andstrengthened academic–community partnerships. Community partners alsocommented on challenges with recruitment, training, and aligningstudent–organization goals.The findings from this study suggest that an update to the Master of PublicHealth program curriculum, its core competencies, a combination ofcommunity-engagement activities, and future evaluations will be needed toadvance education delivery. In fact, students in health professions reported an increased interest inpublic health training and careers during the COVID-19 pandemic, emphasizing the important role that the postsecondary institutions serve indelivering public health education and preparing individuals to enter a wide rangeof roles centered around disease prevention and health promotion. Globally, the demand for skilled public health professionals has beenexpressed by the fact that many regions across the world have already developedaccredited programs or are currently in the process of developing programs forpublic health training.59 The World Health Organizationin partnership with the Association of Schools of Public Health in the EuropeanRegion, has proposed a competency framework that is intended to be used for manypurposes, but mainly to design curricula for professional development anddegree-granting programs. The framework outlines 84 public health competencies categorized into 10 sections. Broadly, competencies are a combination of attributes, knowledge, and skillsrequired to take on a position and outlining these competencies help a region orfield guide and strengthen education.10. Competency-based programsensure that there is an organizational structure for curriculum development,guidelines, consistency in the delivery of a high-quality training, and graduatesfrom these programs can apply skills to deliver essential public healthoperations.1012There is no shortage of complex public health issues and a need for professionals whocan contribute to protecting and improving the health of communities.11 Public health institutions inthe United States and Canada independently outline core competencies for publichealth and Master of Public Health (MPH) graduates, and many of these competenciesoverlap.14 Fortunately, many core competencies  can be trained through traditional coursedelivery methods.16 However, there are concerns that traditional delivery methodsalone may be insufficient to develop skills to the degree required of traineesentering the public health workforce.3 Moreover, competencieshighlighting the importance of skills such as strengthening partnerships,collaborating with community partners, and building community capacity to protectand promote public health may not be readily learned or experienced throughconventional lectures.17 Based on public health’s service to community, it is generallyagreed that community engagement is essential in guiding public health efforts, andis defined as the mutual exchange of resources and information between public healthand community members to develop a sustained partnership.17 This sustained partnershipleads to shared public health responsibility and facilitates changes in behaviors,programs, environments, and policies.19 Therefore, supplementingcurricula to increase coverage of all core competencies provides the motivation forintegrating community-engaged learning (CEL) within public health education.Public health competencies vary across countries because it must serve the localpublic health needs of a population. As a result, CEL can enhance academic outcomes, build professionals’ skills,and foster deeper academic–community partnerships that may not be possibleotherwise.20 Some evidence has indicated that both community partners andstudents value CEL in public health.21 However, there may also becore competency gaps in Canada’s MPH programs, and although unclear, this limitation may be overcome by thecommunity-engagement component of MPH programs. This lack of clarity has led tocalls for investigations to evaluate public health student learning outcomes, assesscommunity partner benefits of CEL, and explore community partner workforce needs tobuild and strengthen partnerships.13 Therefore, there is a need torank various CEL activities and explore perspectives to cultivate a greaterunderstanding of its ongoing effectiveness on public health training.CEL at its core involves matching students with community partners to facilitatestudent learning in communities where they apply knowledge and skills outside of the classroom. This is translated to protecting and promoting health of communities,preventing disease, and prolonging life. A precursor to improvement of communityhealth is public health training to meet community demands. It is believed thatCEL in the form of experiential and in-service training is an important part ofpublic health education.22 However, no study to datehas extensively evaluated and published findings from multiple CEL activities inMPH programs in Canada to comment on the value that CEL has in current graduatepublic health training.According to the World Health Organization, a strong and ready workforce thatcontributes to public health is one of the foundations of global sustainable development.The objectives of this study were to conduct a mixed-methods investigation to:(a) administer a questionnaire to assess students’ self-reported change inlearning outcomes after completing four CEL activities and (b) explore studentand community partner perspectives of CEL through focus groups and interviews. Amixed-methods approach was used to triangulate findings and provide added depthto the quantitative component. These outputs will ultimately contribute toadvancing public health by addressing the upstream prerequisites of developing askilled public health workforce. Findings from this study will reveal strengthsand gaps of CEL in public health training, identify areas for furthering publichealth education, and propose recommendations for strengtheningacademic–community partnerships. This sequential mixed-methods approach helped to achieve the study aimsthrough quantitative identification of the extent to which self-reportedlearning outcomes improved after completing CEL components, qualitativeexploration of how some CEL activities may be more effective through participantdiscussions, and combination of the two approaches to strengthen the evaluationwhich provide insights into education and academic–community partnerships.This study used an explanatory mixed-methods design involving three components:(a) survey of graduate students, (b) qualitative focus group discussion with asubset of students who participated in the survey, and (c) semi-structuredinterviews with host agency community partners. We used a mixed-methods approach because the individual methods on theirown had inherent limitations. Supplementing surveys with a focus group andinterviews allows for cross-examination of results, enhance the depth andbreadth of the research inquiry, prevent potentially missed results from onemethod only, and identify potential avenues for research and practice. In theabsence of a widely accepted mixed-methods reporting checklist, we followedestablished reporting guidelines for qualitative research, and this is availableas Supplemental Material.Explanatory mixed methods use a quantitative component, followed by one or morequalitative components to generate interpretations, and strengthen findingsbased on both components.All members of the research team were affiliated with the educational institutionand directly or indirectly affiliated with the MPH program at the time of datacollection. All research team members were made up of men and women who werepublic health researchers or researchers in training. Furthermore, all weretrained in quantitative and qualitative research methods. The research team hadpreviously developed relationships with study participants, and participantswere aware of the research objectives along with the public health andpedagogical interests in the study. We adopted a pragmatic worldview to approachthe research question, instrument development, data collection, analysis, andreporting of this study. This worldview is compatible with mixed-methods designsand aims to use any approach, tool, or method to help answer the research objectives.25 The 36 core competencies are organized under 7categories: public health sciences; assessment and analysis; policy and programplanning, implementation, and evaluation; partnerships, collaboration, andadvocacy; diversity and inclusiveness; communication; and leadership . The competencies form a set of knowledge, skills, and attitudes to bepracticed by professionals within the public health sector.This investigation was conducted at the University of Guelph in SouthwesternOntario, Canada. The University of Guelph MPH program was formed in 2008 inresponse to the societal need for increased graduate-trained human resources inpublic health. The program was designed in compliance with the Public HealthAgency of Canada’s (PHAC) Core Competencies for Public Health and guidelines forMPH programs.The MPH program at the University of Guelph uses multiple CEL opportunities: (a)a 12-to 16-week practicum placement where students work with and support apublic health organization by focusing on a major project; (b) an application ofpublic health practice tools in-class for case studies or assignments; (c) apublic health capstone course which involves the development of public healthmaterials, knowledge translation, and presenting practicum placement outcomes topeers and public health professionals; and, (d) an applied public healthresearch component which is a supervised research project where the studentinvestigates a public health issue, performs analysis, interprets healthinformation, and prepares a final report.To be eligible, all participants were older than 18 years of age and had to beregistered MPH students or community partners who were currently hosting or hadpreviously hosted MPH students for a practicum placement. All eligible studentswere active full-time or part-time graduate students of the MPH program to meetour inclusion criteria. Alumni and future students were not eligible toparticipate. Community partners were identified through a living database thatwas managed by the MPH Program Coordinator. To be eligible to participate,community partners had to be employed at the organization at which they hostedMPH students during the data collection period. Community partners were alsorequired to oversee some or all aspects of MPH students’ practicum placement tobe eligible for inclusion.Data collection was conducted between December 2016 and January 2017. This periodwas selected because it marked the end of the fall term and the beginning of thewinter term, and therefore, concluding practicum placements or beginning newplacements. The surveys, focus group discussion, and in-depth interviews wereconducted in English.Supplemental Material.A purposive sampling approach was employed based on the inclusion and exclusioncriteria. Recruitment emails were sent to all active MPH students who hadrecently participated in ⩾1 of the following: public health practicum, appliedpublic health research course, public health administration course, or in-classcase studies. The email included a letter of information outlining the scope ofthe project, participants’ rights, confidentiality, and details on consent.Embedded within the recruitment email were links to four online surveys hostedby Qualtrics . Individualscompleted a series of questions regarding their practicum experience ,proficiency in core competencies , andother components of CEL . The questionnaire and other data collection instruments usedin this study were adapted from previously developed unpublished internalquestion guides, pretested on approximately 10% of the targeted studypopulation, and later refined through discussion. The estimated time forcompletion of each survey was 20–30 min, all responses were anonymous, and acopy of the questionnaire is provided as  According to previous research, there is no consensus on the number ofparticipants needed for qualitative research studies and it is suggested thatthematic or data saturation should be emphasized to ensure that all key pointsof discourse are covered.27 Therefore, we aimed fordata saturation across the focus group and one-on-one interviews. Focus groupmoderators and interviewers were previously trained in qualitative datacollection techniques. A copy of the focus group question guide is available asSupplemental Material.Respondents from the survey were invited to participate in focus groupdiscussions on campus. Individuals who indicated interest were providedinformation on participating and consent. Upon arrival to the focus group,participants were made to read details on consent and asked to sign a consentform. This session lasted for 1 h and was moderated by one member of theresearch team, with three others co-moderating and writing notes during thesession . During the session, students were asked to comment ontheir involvement and experience in any four of the CEL activities delivered bythe MPH program. Due to confidentiality purposes and to protect participants, weopted to write notes throughout the discussion on key topics rather than recordthe audio of the session. Therefore, no transcribing was conducted and datacollection was informed by a less intrusive note-taking approach by focus groupco-moderators. Only one focus group discussion was carried out due to lowstudent interest in this component. A similar study exploring MPH students’perspectives about education delivery revealed that depth and data saturationwas met with just six participants.Supplemental Material.After completion of the focus group, an email was sent to community partners whohad hosted University of Guelph MPH students on multiple occasions. Agencies whoagreed to a one-on-one telephone interview were contacted by the research teamvia email to confirm a date and time and were asked to provide written consentprior to the start of the interview. Interviewees were reminded that only noteswould be written by the interviewer, calls would not be recorded and thereforeno transcripts would be made available, and their responses would remainanonymous. All interviewees answered a series of questions regarding theirexperience in hosting graduate students for practicum placements and theirperspectives on CEL. Both data and thematic saturation of qualitative interviewsand the focus group discussion were reached early on, as there were nocontentious topics or substantially different experiences. Telephone interviewsranged between 10 and 15 min, and a copy of the interview guide is accessible as Any “not applicable” responses were excluded from the analysis.Descriptive statistics were evaluated to summarize data. Next, Wilcoxonmatched-pairs signed-rank tests were performed, and the difference in mean rankswere estimated to assess potential changes in respondents’ self-reported corecompetencies before and after completing a CEL activity. This test statistic wasselected because we were analyzing nonparametric paired data. We calculated a minimum required sample size of 21 which was based onpreviously established sample size calculations and the following parameters:α = 0.05, power of 90%, detecting p’ of 0.85, and no ties. Total survey respondents recruited for this study was 25, which exceededthe required minimum. All statistical analyses were performed using STATA/SE 14.Survey responses were exported from the online survey platform and imported toMicrosoft Excel . Each respondent was asked toanswer the same question both before and after their CEL experience regardingtheir subjective level of skill in the selected core public health competencies. Responseswere in Likert scale and assigned a value between 1 and 4. We intended to descriptively summarize qualitative findings and generatethemes that encompass prominent and recurring topics across students andcommunity partners. Trustworthiness of focus group qualitative findings wasenhanced by including some members of the research team who were MPH students atthe time of data analysis. Member checking was not employed for the analysis ofcommunity partner interviews. No statistical software was used in the analysisof qualitative data.Qualitative data were analyzed by four members of the research team . Some elements of reflexive thematic analysis were borrowed whichinvolved the following steps: data familiarization process, a semantic approachto coding, and peer debriefing of salient topics that arose during discussionsfrom the focus group and community partner interviews.Written informed consent was collected from all participants in the respectivesurveys, focus group discussion, and semi-structured interviews. Furthermore,survey responses were anonymized and could not be traced back to the originalrespondent to protect the participant and reduce the likelihood of socialdesirability bias. Although the quantitative component used an anonymous onlinesurvey format, we acknowledge that participants from the qualitative componentsmay have provided more conservative or favorable responses due to preexistingrelationships between researchers and study participants. To promote candidresponse, all individuals were reminded verbally and in writing thatparticipation in this study would not affect their relationship with theacademic institution, MPH Program Coordinator, and that their responses wouldnot be traced back to them. This study was reviewed and approved by the ResearchEthics Board at the University of Guelph (REB#16-JL-037).Supplemental Figure A1), in-class case studies , program development capstone assignment, and applied public health researchcomponent  can be accessed in the Supplemental Material.Overall, 25 out of the 50 MPH students contacted responded to the survey, whichresulted in a 50% response rate and meeting the minimum required sample size forthis study. Although demographics for the student survey were not collected, thetypical MPH student cohort for this institution in recent years haspredominantly identified as women, White, and under 30 years old (>50%).Generally, all four CEL activities improved graduate students’ self-reportedself-efficacy, problem-solving, critical thinking, leadership skills,interpersonal skills, verbal communication, and written communication.Horizontal bar charts depicting self-reported skill development after the publichealth practicum  in addition to the gaps in leadership, communication, and diversityand inclusiveness. Two studies assessing Canadian MPH programs arrived at similarconclusions where authors found that program curricula emphasized public healthsciences compared to other competency categories and new paradigms.35 However, these studies also vary in the outcomes andcompetencies studied, making it challenging to corroborate findings. Regardless, itis unlikely that any single practice-based or in-class course component effectivelyresults in knowledge acquisition and confidence in all public health corecompetencies. Rather, each CEL can focus on only a few competencies, and thus,participation in multiple valuable CEL experiences can allow students to gain skillsacross different competencies to ensure strong education, student satisfaction,academic–community linkages, and professional development.21 Further research is needed toidentify how CEL activities address core competencies differently and whichcombination(s) of CEL opportunities result in the most comprehensive coverage ofskills and public health core competencies.Regarding CEL activities, the largest self-reported core competency improvementsamong students in our study were experienced through the public health practicum.This was highlighted in the fact that most conversations from the focus group andinterviews revolved around the practicum placement. Typically, a public healthpracticum in Canada lasts 12–16 weeks and requires students to work full time with acommunity partner. This immersive experiential learning component may facilitateincreased frequency and magnitude of core competency development compared to otherCEL activities. However, the duration and immersion of CEL activities vary, makingthem challenging to compare. Based on our study findings, it appears that all fourcomponents studied demonstrate benefits in slightly different competencies. Previousresearch assessing MPH program’s learning outcomes reported increases across manytopics and competencies. It is this engagement that contributes to community-engaged scholarship andmutual academic–community benefit.36 Similar to our findings,other studies show that CEL improves skill development among students, networking,organizational capacity, and deepens academic–community relationships.37 The publichealth practicum’s value is through experiential learning that results in thecommitment to community, and others advocate for the benefits of integratingcommunity engagement within public health training.21 Although CEL was perceived assuccessful by all parties in our study, some community partners identified needssuch as extending the period of placements to ensure project completion andchallenges in aligning student needs with the organization. Academia can demonstrateits commitment to the community and strengthen existing relationships by integratingperiodic student and community partner assessments throughout practicum placements.These evaluations can identify ongoing student–community challenges to proposeproactive solutions or program-wide changes to meet community needs and betterprepare the next generation of public health professionals.In the 1996 seminal essay, Ernest Boyer stated that scholarship of engagementinvolved connecting academia with society, continuously and creatively collaboratingwith each other to answer important social, civic, economic, and moral problems.39 For instance, competencies from low- and middle-incomecountries may not apply to high-income countries. Globally, several regions have adopted their own public healthcompetencies or are in the process of drafting them to support MPH and otherpublic health training.3841 Generally, there are manyshared competencies across countries such as policy planning and development,leadership, collaboration, communication, advocacy, and systemsthinking.40 These make up the core public health skills andattributes necessary to create a unified and strong public health workforce. Thepresent study only evaluated change in competencies after CEL activities from aprogram in Canada, but some of these findings may also apply to a broadercontext. For instance, a multicountry study assessing MPH programs in China,Mexico, the Netherlands, South Africa, Sudan, and Vietnam revealed that MPHgraduates who indicated that their graduate program enabled them tosubstantially apply various core competencies ranged between 33% and 48% withpolicy development competencies being rated the lowest. Furthermore, a qualitative study from the United Kingdom exploringstudents’ experiences found that MPH students wanted more options to increasetheir employability. This suggests that current program curricula may not be achievingoptimally intended competency-based training for public health graduates.Combined with the findings from our study which revealed that each of the CELactivities provided discrete benefits of: (a) general work-related skills suchas critical thinking, problem-solving, and self-efficacy and (b) corecompetencies such as policy, leadership, and public health sciences, it islikely that multiple CEL activities must be integrated into MPH programs tosupplement traditional course delivery.Public health competencies vary across countries because skills and attributesneed to be context specific and cater to the demands of the localpopulations. We found that CEL activities improved self-reported learning outcomes,and each CEL activity favored certain core competencies. Our recommendationsinclude amendments to curriculum, CEL, and evaluations. First, public healthcurricula can consider the following to advance graduate training: implementinga mandatory community-engagement component, encouraging faculty to adopt CELinto their teaching strategy, refreshing MPH programs to implement currentworkforce needs , and increasing coverage ofcompetency gaps by integrating them into existing course offerings. Second, our study providesfurther rationale for increasing the emphasis on community engagement in MPHprograms,42 overcoming barriers faced by community partners whocurrently participate or intend to participate in CEL, coordinating multiple extended CEL opportunities to ensure development ofvarious core competencies, and periodically assessing CEL activities to identifyareas for improvement to achieve a well-balanced graduate training that coversall core competencies. Lastly, investing in infrastructure to conduct ongoingevaluations of public health program components, CEL activities, and entire MPHprograms can promote knowledge transfer and strengthen education deliveryespecially if they are publicly disseminated.13 Using a combination ofthese may overcome existing teaching and learning core competency gaps,strengthen academic–community partnerships, and identify current student- andworkforce-specific needs to further public health training and quality ofeducation delivery.CEL helps to further student learning, address community concerns, may improvedepartmental scientific rigor, and enhance applied research in public health.First, the study draws on data from a small sample size using non-probabilitysampling, which has the potential to invite biases. However, the aim of thisstudy was to evaluate learning outcomes and explore community-engagementapproaches to education rather than establish generalizable parameters.Furthermore, we reached minimum sample size requirements in the surveycomponent, and thematic saturation in both the focus group and one-on-oneinterviews. The mixed-methods assessment allowed to overcome some of theindividual component limitations, facilitated cross-comparison of these results,and strengthened the overall findings. Secondly, we used anonymous responses inthe survey methods, but the qualitative components required direct interactionbetween the research team and study participants. However, this also enhancedour ability to collect extensive data and facilitate richer discourse in thefocus group and interviews. Thirdly, we did not record any audio from the focusgroup and telephone interviews due to confidentiality and to promote openresponses, but as a result, there were no illustrative quotes to supportqualitative findings. Future investigations should attempt to invite participantvoices while still protecting anonymity to build on this study. Lastly, the datawere collected before the COVID-19 pandemic and there are some concerns aboutexternal validity and whether the findings are generalizable beyond the contextand duration of the study. However, many, if not all, of the study findings maystill apply today because there have been no changes made to the Canadian publichealth core competencies in nearly 15 years. Regardless, an update to thisassessment may provide insights into how CEL has been impacted during theCOVID-19 pandemic, and how training can respond to public health crises.This mixed-methods study assessed MPH students’ self-reported student learningoutcomes, experiences with multiple community-engagement components, andtriangulated findings through community partner interviews. Students reported largeimprovements in some competency categories such as public health sciences, and gapsin others such as leadership. Students and community partners experienced severalbenefits from community-engagement learning ; but also identified needs .This study demonstrates the effectiveness of using a combination ofcommunity-engagement learning activities to increase coverage of public healthcompetencies.Going forward, MPH graduate curricula and existing public health core competenciesmust be revisited and modified to enhance learning outcomes and create a preparedworkforce. Workforce demands, community needs, and student expectations must also beconsidered when making changes to the curricula. We recommend future researchexplore solutions to the student and community barriers identified in this study andpublish evaluations of public health programs in other institutions and regions.Click here for additional data file.Supplemental material, sj-doc-1-smo-10.1177_20503121231176637 for A mixed-methodsassessment of community-engaged learning in a Master of Public Health program byAbhinand Thaivalappil, Rachel Coghlin, Courtney Bell, Brendan Dougherty,Stephanie Duench, Rachelle Janicki and Andrew Papadopoulos in SAGE OpenMedicineClick here for additional data file.Supplemental material, sj-docx-2-smo-10.1177_20503121231176637 for Amixed-methods assessment of community-engaged learning in a Master of PublicHealth program by Abhinand Thaivalappil, Rachel Coghlin, Courtney Bell, BrendanDougherty, Stephanie Duench, Rachelle Janicki and Andrew Papadopoulos in SAGEOpen Medicine


The acceptance of nanoparticle technology in the quest for cancer treatment is due to its many potentials and possibilities of filling in the gaps in the limitations of the current treatment modalities. Insights into the possibilities of getting even more from this technology, as well as the synergistic properties of photothermal therapy (PTT) and photodynamic therapy (PDT)—the use of reactive oxygen species (ROS)—can also be exploited in the ablation of prostate cancer tumors. Therefore, the combination of gold and selenium photoactive nanoparticles as platforms for drug delivery via PTT/PDT in prostate cancer therapy, with a specific emphasis on the 'micro-carrier' based approach, was discussed and explored in this review under relevant subtopics ranging from understanding the complex chemistry and biology of the pharmacologically active Se/Au-containing agents to giving a thorough knowledge of these therapeutic agents' potential as a targeted and successful treatment strategy for prostate cancer by investigating the complex mechanisms behind their delivery, activation, and synergistic effects. Furthermore, this article presents a comprehensive overview of the current research environment, problems encountered, and future perspectives in the continuous war against prostate cancer. Prostate cancer is a prevalent disease that constitutes a significant contributor to mortality rates associated with cancer among males on a global scale . The conGold nanoparticles have distinct photoactive characteristics that facilitate accurate tumor localization and localized hyperthermia . The curAccording to a study conducted by , there iThe synergistic interplay of selenium nanoparticles (SeNPs) and gold nanoparticles (AuNPs), along with their straightforward production, cost-effectiveness contributes to their many advantages and their high surface-to-volume ratio, facilitates their easy infiltration into tumor sites via the enhanced permeation and retention (EPR) phenomenon. Selenium nanoparticles (SeNPs) can induce the generation of reactive oxygen species (ROS), which can function as an additional mechanism for suppressing tumor growth. The combined effect of these components boosts the effectiveness of thermal energy dissipation in the designed capsule. Consequently, this combined effect of SeNPs and AuNPs yields a dual pharmacological effect and enhanced photothermal conversion efficiency , 3, 5.The findings from both in vitro and in vivo experiments demonstrate that the combined use of photothermal treatment (PTT) and reactive oxygen species (ROS)-mediated therapy has a superior capacity to inhibit tumor growth compared to monotherapy approaches based on either selenium or gold-filled caps alone. In addition, the hybrid carriers have minimal in vivo toxicity towards vital organs like the heart, lungs, liver, kidneys, and spleen, as indicated by previous research . The proThe objective of this review article is to present a thorough overview of existing studies pertaining to the use of selenium and gold in delivery systems for the combined application of ROS-mediated photodynamic treatment (PDT) and photothermal therapy (PTT) in the context of prostate cancer. And, to provide a comprehensive understanding of the underlying principles of photothermal treatment, elucidate the role of reactive oxygen species (ROS) in cancer therapy, conduct a thorough examination of the mechanisms involved in nanoparticle transport, analyze the design and production of microcarriers, and assess their potential impact on enhancing therapeutic effectiveness. This paper aims to critically examine current advancements in microcarrier design, targeting methodologies, and therapeutic outcomes, with the objective of offering valuable perspectives on the potential of these emerging delivery systems to revolutionize the field of prostate cancer therapy.A comprehensive understanding of the multimodal properties of selenium and gold-incorporated polymer-based microcarriers in the context of prostate cancer treatment is presented. Specifically, the article explores the potential of these therapeutic agents as a targeted and effective strategy for prostate cancer treatment by examining the intricate mechanisms involved in their delivery, activation, and synergistic effects in ROS-mediated combination photodynamic therapy (PDT) and photothermal therapy (PTT).This review explores the intricate relationship between nanoparticle delivery pathways, tumor microenvironment, and therapeutic efficacy in prostate cancer cells with a specific emphasis on the 'micro-carrier' based approach. It highlights challenges and strategies for improving microcarrier design, focusing on recent papers published within the last 4 years.This review summarizes publications pertaining to the subject matter. Keywords include "gold nanoparticles", "selenium nanoparticles", "photothermal therapy", "reactive oxygen species", and "photodynamic therapy". PubMed, Google Scholar, Web of Science, and Scopus were used to source quality peer-reviewed articles from 2018 to mid-2023. Clinical study data was obtained from the official website clinicaltrials.gov. This study holds significance as it highlights relevant research on the use of AuNP/SeNP microcarriers for the purpose of photothermal and ROS-mediated combination therapy in the context of prostate cancer. The objective of this study is to provide a comprehensive overview of recent advancements in the field of chemical modification, architectural design, and latest innovations of gold nanoparticles (AuNPs) and selenium nanoparticles (SeNPs) as microcarriers for reactive oxygen species (ROS)-mediated combination therapy targeting prostate cancer tumors.Prostate cancer is widely recognized as the second most common disease affecting males worldwide, with significant variations in both incidence and mortality rates across different populations . The disThe prostate gland is an anatomical structure inside the male reproductive system that is located inferior to the bladder and surrounds the urethra. The majority of prostatic tumors exhibit a slow progression but there is a potential for cancer to metastasize to other organs, particularly the lymph nodes and skeletal system. Initially, individuals may not exhibit any symptoms whatsoever. Over time, individuals may experience symptoms such as dysuria, hematuria, or lumbopelvic pain with the progression of the condition . ProstatMultiple factors, such as a familial predisposition to prostate cancer and various environmental influences, contribute to an increased susceptibility to developing prostate cancer or progressing to a more aggressive form of the disease. Inherited genetic factors contribute to around 10% of prostate cancer cases and 40% of early-stage prostate tumors . Tumors To find any gaps in clinical needs and produce new ways to treat prostate cancer, it is important to have a full understanding of where it occurs, how common it is, and what it means for patients. Therefore, to enhance public consciousness regarding the potential risks associated with prostate cancer, the Obama administration officially declared September Prostate Cancer Awareness Month .Medical surgery: Radial prostatectomy is a surgical procedure that involves the complete removal of the prostate gland and the surrounding tissues. The use of this treatment modality is considered a viable therapeutic option for the management of locally advancing prostate cancer .Radiation treatment encompasses a range of procedures, which include:External Beam Radiation Therapy (EBRT) utilizes high-energy proton beams to eradicate cancer cells located in the prostate. Localized prostate cancer is frequently treated using this method, which can also be employed alongside other therapeutic interventions .Brachytherapy involves the localized insertion of little radioactive seeds into the prostate to deliver radiation to the tumor as a therapeutic intervention. The utilization of this approach is commonly observed in the management of localized prostate neoplasms with a low-to-moderate risk profile .Luteinizing hormone-releasing hormone (LHRH): A luteinizing hormone-releasing hormone (LHRH) agonist is a type of medication that stimulates the release of luteinizing hormone. These drugs function by reducing the levels of testosterone, a biochemical compound that promotes the development of prostate cancer. Typically, these treatments are administered through injections or implants lasting several months or years.Anti-androgens: Anti-androgens are pharmaceutical agents that inhibit the biological activity of testosterone within the human body. They are commonly employed in combination with Luteinizing Hormone-Releasing Hormone (LHRH) agonists to augment the suppression of testosterone ,Combined androgen and LHRH agonists blockade: The therapeutic strategy known as combined androgen blockade entails the combination of LHRH agonists with anti-androgens to achieve a more comprehensive blockade of androgen activity . EnzalutAndrogen Deprivation Therapy (ADT) is a medical intervention that impedes the endogenous production of androgen hormones, including testosterone. The transduction cascade of the androgenic receptor (AR) plays a significant role in the development and advancement of prostate cancer .LuteinizCurrent conventional therapies for prostate tumors include medical surgery, irradiation, and treatment with androgen deprivation . DespiteIt is important to understand that the above constraints are not absolute for all individuals and may differ based on individual circumstances such as cancer phase, grade, and general well-being.Given the constraints of existing treatment modalities, there is an urgent need for innovative therapeutic techniques that have been shown to improve clinical outcomes, minimize adverse effects, and overcome resistance. The adoption of selenium and gold-incorporated polymeric carriers offers a promising avenue for the development of an innovative approach to prostate cancer treatment. Nanoparticle technology enables the targeted delivery of high drug loads to specific sites, hence reducing the risk of adverse effects, prolonging the half-life of the transported therapeutic component and mitigating resistance to various treatments in malignant cells –24. A diWithin the realm of nanomaterials, it has been suggested that selenium nanoparticles (SeNPs) possess the highest level of promise, as they exhibit exceptional attributes for combating cancer and demonstrate favorable physiological compatibility , 36. SelSeleniumSelenium (Se) was first discovered by Jöns Jacob Berzelius during the early nineteenth century. It was classified as a chalcogen and placed in group 16, alongside oxygen, sulphur, tellurium, and polonium . During 2−), elemental selenium (Se0), selenites (SeO32−), and selenates (SeO42−). In biological systems, selenium is present as selenocysteine and seleniomethionine  de de87] deThe researchers used Au-silica nanoparticles for the purpose of conducting ultra-focal photothermal ablation as a treatment option for prostate cancer . The useGold nanoparticles (AuNPs) have garnered significant interest as a promising option in the co-administration of drugs, photothermal therapy (PTT), and photodynamic therapy (PDT) in the management of prostate cancer. The ongoing clinical trials with gold nanoparticles (AuNP) highlight their potential significance in translational research and their potential efficacy in eradicating prostate tumors.Gold AuroShell nanoparticles were assessed in clinical studies for the treatment of prostate cancer. The initial study, published in 2015, revealed the absence of any enduring adverse effects . In a suThe current clinical trials involving gold nanoparticles within the framework of gold and selenium photoactive nanoparticles for drug delivery by photothermal therapy (PTT) and photodynamic therapy (PDT) in the treatment of prostate cancer highlight their increasing translational significance and potential for therapeutic efficacy.  light exhibits significantly lower energy levels compared to higher-energy radiation such as ultraviolet (UV) light. Consequently, NIR light possesses the ability to efficiently facilitate tissue healing and penetrate deeper into cellular structures . TypicalNotably, only nanoparticles characterized by simple surface functionalization process, high photostability, plasmon resonance tunability, and high photothermal conversion efficiency should be used in PTT . TherefoThe PTAs (AuNPs and SeNPs) absorb NIR, causing the malignant cells to become hyperthermic. Following a series of stages, this elevated temperature in the cancer microenvironment induces apoptosis. This is adapted from .An improved approach to drug delivery for photodynamic therapy (PDT) and photothermal therapy (PTT) in the context of prostate cancer treatment has been achieved through the incorporation of gold and selenium photoactive nanoparticles onto microcarriers. In order to enhance the precise and regulated administration of therapeutic agents, it is critical to understand the various drug release mechanisms associated with these microcarriers.Temperature-controlled releaseAdding gold nanoparticles to the microcarrier matrix makes it possible for drugs to be released by photothermal means (carrier shrinkage) when the temperature rises. When gold nanoparticles are exposed to near-infrared light, they cause localized hyperthermia. This can change how therapeutic payloads are released, leading to a precisely controlled and on-demand drug delivery profile [ profile , 101.2.Redox-responsive releaseUsing selenium-based nanoparticles in microcarriers to increase the levels of reactive oxygen species (ROS) inside cells can help release drugs that is responsive to redox conditions. Due to their redox-sensitive properties, selenium nanoparticles can release therapeutic compounds precisely when prostate cancer cells are under oxidative stress [e stress . This ree stress .3.Enzyme-triggered releaseEnzyme-responsive scaffolds in microcarriers can produce enzyme-triggered drug delivery in the tumor’s milieu. Overexpression of enzymes in the tumors surroundings can accelerate the destruction of the delivery system matrix, resulting in the regulated dispersion of drug contents [contents . This encontents .4.Light-activated releasePhotoactive materials packed into the microcarrier design allow for light-triggered drug release in response to certain wavelengths of light utilized in PTT and PDT. When exposed to light, photo-sensitive binders or cross-linkers can be cleaved or undergo re-structuring, promoting the release of packed drugs [ed drugs . This lied drugs .5.pH-dependent releaseMicrocarriers made of pH-responsive materials can be used to release drugs in an acidic environment inside a tumor. The acidic pH of cancer cells could change their structure or destroy pH-responsive delivery platforms, which would allow cancer drugs to be released in a controlled and targeted way [eted way . This pHeted way .6.Diffusion-controlled releaseThis is a basic mechanism found in numerous microcarrier systems. The variation in concentration and the diffusion coefficient of the drug inside the carrier matrix primarily influence the drug release rate [ase rate . The porase rate .7.Degradation-controlled release.Certain microcarriers contain biodegradable polymers that decay over time, allowing enclosed drugs to be released gradually. The degradation-controlled release approach enables fine control of release kinetics and drug delivery duration [duration . The breduration .8.Stimulus-responsive releaseFor drugs to be released from microcarriers in a stimulus-responsive way, they have to be released when certain environmental stimuli are present. Changes in pH, temperature, or enzyme activity can be used to control therapeutic drug release in the target region [t region . This tet region .The nanoparticle delivery pathway for photoactive selenium and gold nanoparticles must be understood in order to develop systems for delivering pharmaceuticals to individuals with prostate cancer in a targeted and efficient manner. Enhancing the delivery method of nanoparticles in order to optimize the targeting and efficacy of PTT/PDT paves the way for the development of more effective and individualized treatment approaches.The distinct optical features and strong biocompatibility of gold nanoparticles (AuNPs) make them potential therapeutic platforms for targeted and image-guided treatment in cancer therapy.Role of gold and selenium photoactive PTT/PDT nanoparticles in drug delivery in prostate cancer therapy: Gold and selenium photoactive nanoparticles have become flexible ways to deliver drugs when used with both photodynamic therapy (PDT) and phototransduction therapy (PTT). These nanoparticles absorb alight in the near-infrared range, allowing for an effective conversion of light energy into heat and producing localized hyperthermia at the tumor’s location [location . Also, slocation .2.Enhanced targeting and selective treatment efficacy: These tiny gold particles and selenium photoactive particles make it easier to target and treat prostate cancer when they are used as drug delivery platforms in PTT and PDT. These nanoparticles may be functionalized by targeting ligands such as antibodies or peptides to allow for targeted interactions with cancer cells, reducing off-target effects and increasing therapy results [ results . The syn results .3.Clinical trials and translational potential: Several preclinical studies have shown that AuNP-based PTT is a safe and effective way to treat prostate cancer. Using AuNPs along with PTT/PDT in clinical studies is currently being carried out to study treatment response, disease progression, and long-term outcomes in men with prostate cancer [e cancer . These tPhotothermal treatment offers a few benefits, including precise tumors targeting, negligible obtrusiveness, and the potential for combinatorial therapy. In any case, issues involving restriction of penetration of light by tissues, loss of heat, and harm to surrounding cells and tissues should be monitored. New AI and computational approaches may offer even more optimization . This isThe main benefit of PTT is that the photo-responsive materials only reach the tumors, raising the temperature without having much of an effect on the healthy cells and tissues nearby . The selPTT exhibits some drawbacks that must be addressed to ensure smooth clinical integration. These are: (a) poor focusing capability and photoactive agent flaws; (b) weak photothermal impact; and (c) potential heat harm to healthy cells . PTT hasNanoparticles (NPs) with a 100-nm diameter are capable of penetrating cancerous cells and persisting for an extended period of time . AlthougAnother limitation of PTT is that it has a restricted level of light absorption in tissue structures. As a result, PTT alone fails to be effective enough to eliminate a tumor, resulting in its regrowth and the development of malignancies throughout the human organism . In ordeGold nanoparticles (AuNPs) have gained recognition as valuable photo-active agents due to their distinctive characteristics, including their ability to interact with light, surface plasmon resonance, and ease of modification qualities . The incConsidering the fact that the utilization of gold nanoparticles (AuNPs) and selenium nanoparticles (SeNPs) in photothermal therapy (PTT) has the potential to elicit an immune response against tumors within the human body, it is reasonable to strategically combine this approach with antibody therapy. This can be achieved by administering immune-stimulating drugs, such as PD-1 immunological checkpoint inhibitors, in conjunction with the aforementioned nanoparticles .2. Additionally, rare earth elements such as AuNrs, Au nanoplates, and Au–Ag alloys are included in this category [An alternative approach to enhancing the efficacy of a Photothermal therapy (PTT) agent involves combining two or more PTT agents. This development is expected to enhance the photothermal efficiency of photoactive materials. The aforementioned materials include carbon-based materials such as graphene and carbon dots, as well as semiconductor nanoparticles like CuS, CuSe, and MoScategory , and cercategory . The intcategory .A substantial number of studies on microcarriers made up of various inorganic and organic nanoparticles have been conducted in recent years . The mosGold nanoparticles (AuNPs) of various shapes are among the most widely recognised photoactive nanoparticles for PTT, according to previous studies. This is due to their high surface plasmon resonance and ability to convert light into heat . InteresAccording to a study , A compuCurrently, the design of drug delivery systems, in the field of material science and development, mainly depends on the researchers' intuitive judgement and traditional trial and error methods. AI has the potential to automate and make processes like nanoparticle design and optimization more efficient. This includes tasks such as modelling, stability assessment, and efficacy analysis. In addition, AI can enhance real-time cell imaging, provide predictive analysis for drug release kinetics and toxicity, monitor biomarkers and drug levels in real-time to enhance personalized therapy and facilitate multiscale modelling for drug delivery systems , 119.Regarding cancer, oxygen compounds known as reactive oxygen species (ROS) operate as both pro-survival messengers and lethal actors . ROS arelichen induced non-apoptotic cellular mortality in the Cap culture (PC-3) at 2 g selenium per mL, according to [Biological SeNPs derived from Bacillus rding to . This warding to .Photodynamic therapy (PDT) has emerged as a promising non-invasive therapeutic modality for the treatment of prostate cancer. In photodynamic therapy (PDT), certain wavelengths of light activate photosensitizers, which produce singlet reactive oxygen species (ROS). These ROS have cytotoxic effects on cells and destroy tumors. To induce ROS in tumors, many techniques have been devised, including PDT, sonodynamic therapy, and CT . Given tBasic concepts and mechanisms of photodynamic therapyPhotodynamic treatment operates on the principle that triplet states result when photosensitizers are activated by light. By gaining energy, molecular oxygen generates extremely unstable singlet oxygen species and other reactive oxygen species. These induce oxidative damage to cancer cells [er cells , 125. Ther cells .2.Types of photosensitizers for photodynamic therapyIn order to promote personalized therapy approaches and enhance clinical efficacy in prostate cancer PDT, it is critical to comprehend the various properties and mechanisms of action of these photosensitizers.Several photosensitive substances have been studied for their effectiveness in prostate cancer PDT. These photosensitizers have different absorption and emission spectra, which allow for selective activation at certain light wavelengths. Photosensitizers that are extensively used include:Porphyrin-based Photosensitizers: Due to their good light absorption qualities and physiological compatibility, porphyrin derivatives such as protoporphyrin IX (PpIX) and its precursors, Aminolevulanic acid (5-ALA) and Motexafin Lutetium (Mlu) demonstrated encouraging results in PDT for prostate cancer, with efficacy in murine, canine tumor models and human trials. These photosensitizers are effective tumor-targeting agents that may be delivered systemically or topically .Photosensitizers based on Chlorophyll: Chlorophyll derivatives have received interest for their prospective uses in prostate cancer PDT. These photosensitizers are promising candidates for cancer treatment because they have good photochemical stability and produce phototoxic effects when exposed to light. Examples include Pheophorbide .Photosensitizers based on Phthalocyanine: Phthalocyanine derivatives such as silicon phthalocyanine (Pc4) absorb light very strongly in the near-infrared range, which makes it easier to reach deeper into tissue and target tumors. They are interesting candidates for PDT in prostate cancer treatment due to their excellent photostability and efficient ROS production .Photosensitizers under development: Researchers are working on new photosensitizers that are different from the ones that are already available. These include nanoparticles, carbon-based compounds, and organic dyes. Examples include TOOKAD; a vascular-targeted padeliporfin, porfimer sodium, verteporfirin, talaporfin and redaporfin (bacteriochlorin). They are being studied for use in prostate cancer PDT. The targeted specificity, biocompatibility, and photophysical properties of these new photosensitizers can all be changed .Coupling ROS production with PTT has been shown to have collaborative benefits for cancer cell elimination. The photothermal effect causes thermal shock, which increases the generation of cellular ROS. ROS consequently increase hyperthermia's damaging impact by worsening cellular stress and activating cellular death cascades . ROS-medSelenium exhibits antioxidant properties at moderate concentrations; however, when present in excess, it transforms into a pro-oxidant, thereby enhancing the production of reactive oxygen species (ROS). Cancer cells exhibit susceptibility to additional reactive oxygen species (ROS) despite the high abundance of these species and reducing agents within them. , 134.It was demonstrated in  that comBetter Permeation and Retention Effect: The ability of gold and selenium nanoparticles to adhere to tumor cells is due to their favorable physical and chemical characteristics, which confer permeability and retention (EPR) effects. The passive accumulation of nanoparticles in the tumor microenvironment can occur due to the organization of tumor vessels and the compromised functionality of lymphatic drainage . Drugs mReceptor-Mediated Endocytosis: Nanoparticles composed of selenium and gold have the potential to enhance the specificity of ligands or antibodies that target prostate cancer cells with an excessive number of receptors. This receptor-mediated endocytosis enables nanoparticles to enter cancer cells, enabling precise delivery of therapeutic cargo . Using rIntracellular Transport and Subcellular Localization: Gold and selenium nanoparticles are transported within cells via intracellular trafficking pathways. As a consequence, they accumulate within subcellular constituents such as endosomes and lysosomes . PTT andReactive Oxygen Species-Mediated Cytotoxicity: Nanoparticles made of selenium can make cancer cells produce reactive oxygen species (ROS), which can lead to oxidative stress-induced cytotoxicity and cell death through apoptosis. This ROS-mediated cytotoxicity is critical to the therapeutic effectiveness of selenium nanoparticles when combined with PTT/PDT, emphasizing the importance of the nanoparticle delivery mechanism .Heat-Mediated Tumor Ablation and Apoptosis: Gold nanoparticles exhibit remarkable light-to-heat conversion properties when subjected to near-infrared light, thereby facilitating accurate and focused hyperthermia within prostate cancer tumors. The selective destruction of cancer cells while preserving healthy tissues in close proximity can be achieved by heat-mediated tumor ablation and induction of the apoptotic pathway via PTT .Knowledge of the nanoparticle delivery pathway in the context of gold and selenium photoactive nanoparticles is critical in developing targeted and efficient drug delivery systems for prostate cancer therapy.Several metrics are employed to evaluate the therapeutic efficacy of combined photothermal therapy with ROS delivered via selenium and gold-based systems. Tissue shrinkage is assessed through the methodical monitoring of temporal variations in both tumor mass and size. Flow cytometry and immunohistochemistry can be employed to investigate cell death pathways encompassing necrosis and apoptosis. To determine the efficacy of a treatment, alterations in biomarkers that indicate the cancer's stage of progression and drug resistance are monitored .The mechanisms by which ROS-mediated combination photothermal therapy is a more effective treatment have been the subject of increased exploration. The negative consequences consist of the degradation of nucleic material, oxidative stress induced by reactive oxygen species, and disruption of cellular processes that are essential for the development and survival of the tumor. The discovery of the link between ROS production and PTT , 144 hasBlended non-crystalline selenium encapsulated in gold chain oligomers was described in . The Se-The Se-Au chain oligomers were discovered to increase the concentration of reactive oxygen species (ROS) by 36% whenever the readings were compared before and after the NIR irradiation. The photothermal properties of the gold-selenium chain and Se's ability to combat cancer could work together to increase the concentration of reactive oxygen species between cells. Consequently, these exceptionally stable Se@Au chain-oligomers have a promising future as in vivo photothermal therapy agents for prostate cancer and other forms of the disease .In a detailed study , severalBeyond prostate cancer,  describeThe development of microcarriers composed of gold and selenium-containing polymers may improve the delivery of medications to prostate cancer tumors. These biologically compatible polymer frameworks can be designed to encapsulate gold and selenium nanoparticles. Particulate size, surface furnishing, and controlled release capabilities are deliberate design considerations to optimize the accumulation of drugs in tumors and guarantee treatment effectiveness , 143–154Material Selection: Depending on the intended application, the choice of material for microcarrier synthesis is essential. To ensure low toxicity and immunological reactions, biodegradable and biocompatible materials are frequently used for biomedical applications . Common Solvent Selection: Choosing the right solvent is crucial for the synthesis process since it affects the morphology and size of the microcarrier and dictates how easily the components will disperse . Organic Techniques for Synthesis: The method chosen for microcarrier synthesis relies on the material, the desired size, and the morphology . TypicalEmulsion/Solvent Evaporation: In this process, the polymer is mixed with a stabilizer in an aqueous phase. This is done after the polymer has been dissolved in an organic solvent. The subsequent evaporation of the organic solvent results in the creation of microcarriers .Spray drying can be used to produce solid microcarriers from a solution or suspension of the microcarrier material .EHD techniques such as electrospinning and electro-spraying can create microcarriers with precise sizes and morphologies. Using a template, it is possible to generate microcarriers with precise shapes and porosity architectures .Microfluidics: With fine control over size and form, microfluidic devices can create monodisperse microcarriers .Surface Functionalization: Surface functionalization enables extra capabilities, including increased targeting, improved biocompatibility, or sustained payload release. There are many methods for surface modification, including coating with biomolecules, ligand conjugation, and attaching targeted moieties , 87.Drug Loading: A suitable loading method should be used if the microcarriers are meant to transport a payload, such as medications or nanoparticles. Based on the payload and the microcarrier, this may include simple adsorption, encapsulation during synthesis, or surface conjugation .Characterization of the fabricated nanoparticles and microcarrier characteristics: To evaluate their shape, content, and functional groups, methods like scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) can prove useful .After identifying the techniques and resources that other researchers in related subjects have found to be most effective, the selection of suitable materials for the microcarriers and delivery systems is made using simulation and machine learning in combination with literature. Mthematical simulations, machine learning, and literature are all used together. For example, biodegradable polymers, silica, or materials based on carbon can be used as microcarriers, and gold and selenium nanoparticles can be added because of their special qualities . A suitaIf drug distribution is the goal, packing the required drug into the microcarriers and encapsulating it is recommended. To understand the effectiveness of the delivery mechanism, drug release kinetics should be conducted. After that, research on toxicity and biocompatibility should be conducted. If targeted drug delivery is the goal, looking into various targeting techniques to increase the system's ability to deliver the medication precisely to the intended location is required. Finally, planning should be done for testing, validation, optimization, and continual improvement .Even with the promising potentials of selenium and gold-infused polymer-based microcarriers, several issues must be properly resolved to increase their effectiveness for treatment, guarantee effective tumor targeting and permeation, regulate the delivery of drugs and guarantee their practical use clinically; these involve enhancing the physicochemical characteristics of microcarriers, such as size, coating charge, and discharge rates , 151.To overcome drug resistance and enhance the results of therapy, combinatorial therapy and complementary techniques must be developed. To get more benefits and personalized treatment plans, more research should be done on how to combine chemotherapy, immunotherapy, targeted therapy, and microcarriers with selenium and gold in a combinatorial approach , 147. InThe clinical uses and applied benefits of delivery systems developed from polymers with SeNPs and AuNPs for prostate cancer treatment are encouraging , 121. ToSelenium and gold nanoparticles used in polymer-derived delivery design offer a novel and promising approach for ROS-inducing synergized photothermal treatment in prostate cancer. The synergistic effects of ROS generation and photothermal therapy provide a powerful strategy for tumor regression and improved treatment outcomes. However, further research is needed to optimize microcarrier design, explore combination therapies, and evaluate their translational potential. With continued advancements in this field, selenium and gold-incorporated microcarriers have the potential to revolutionize prostate cancer treatment by providing targeted and effective therapeutic options.


The autonomic nervous system is related to involuntary body functions, including gastrointestinal mechanisms, blood pressure, skin muscle activity and heart rate Hall, . The litAbdalbari et al., which applied Granger Causality to capture brain-heart mechanisms during wakefulness and sleep. Granger Causality is a statistical test that can also be used as a measure for bidirectional connectivity in EEG   and its association with VVS. The CGRP is a peptide localized to C and Aδ sensory fibers with important role in sensory and efferent function, which presents a broad innervation throughout the body with large perivascular location , also known as neurocardiogenic syncope or reflex syncope, is an impairment investigated worldwide , root mean square of successive differences (RMSSD), low-frequency power (LF), high-frequency power (HF), and LF/HF. As the main data, heart rate variability was increased by taxane and carboplatin treatment.Another study related to heart rate variability was published by Arai et al. tried to establish a new animal model related to stress cardiomyopathy. The study investigated epilepsy-induced stress cardiomyopathy and the involvement of neuropeptide Y in cardiac dysfunction. The report evidenced that activation of the sympathetic nervous system leads to upregulation of neuropeptide Y in cardiac sympathetic nerves and stellate ganglion.Finally, Takotsubo cardiomyopathy is another pathology involved with the relationship between autonomic injury and cardiovascular risk increase (Amin et al., Briefly, the articles published in this Research Topic provide additional information regarding brain-heart interaction, vagus nerve activity, heart rate variability and stress cardiomyopathy. Therefore, the results obtained in this Research Topic supply compelling evidence that adds valid data to better comprehend the association between cardiovascular risk and autonomic nervous system.VV and LV drafted the editorial and gave final approval.


Lipotoxicity is the dysregulation of the lipid environment leading to the accumulation of harmful lipids that can lead to organelle dysfunction, cellular injury, and cell death. It is often associated with metabolic disease and can occur in many organs, including heart, skeletal muscles, liver, kidney, pancreas, and brain. Although toxic lipids can cause cellular damage through known major mechanisms, it is still unclear how specific lipid classes that directly participate in lipotoxicity contribute to altered cell behavior and mitochondrial bioenergetic functions.Frontiers in Endocrinology Research Topic aimed to identify potential drug targets in the molecular mechanisms behind hyperlipidemia (lipotoxicity)-induced mitochondrial alterations (mitotoxicity). As lipotoxicity is related to altered metabolism and the development of different chronic diseases, such as diabetes, cardiovascular diseases, and neurodegenerative disorders, the goal was to bring forth potential metabolic checkpoints in lipotoxicity-induced cellular dysfunction. This Research Topic puts together different contributions regarding lipotoxicity and mitotoxicity in a broader context of diseases, and also highlights potential therapeutic strategies.Lipotoxicity, Mitotoxicity, and Drug Targets is a Zhou et al. demonstrated by a cross-sectional analysis the significant correlation between serum palmitic acid (PA) and thyroid dysfunction that was more remarkable in male and obese subjects. This finding highlights the close relationship between lipotoxicity and hypothyroidism, or subclinical hypothyroidism, and points towards potential sex-related differences in lipid metabolism and lipotoxicity progression. Further studies are needed to verify the causal association between PA and thyroid function.Although it is clear that metabolic health is dependent on a healthy diet and hormonal homeostasis, studies addressing the link between lipidemia and hormones that regulate energy metabolism, such as thyroid hormones, are limited. In a retrospective study, Zhao et al. provided a systematic review of the causes and mechanisms of insulin resistance, highlighting that mechanistically, any factor  provoking abnormalities in insulin signaling leads to the development of insulin resistance. The role of the accumulation of different lipid classes in the inhibition of insulin signaling (phosphoinositide 3-kinase - protein kinase B) pathway has previously been widely investigated  can accumulate ectopically and adversely altered the function of different organs. This mechanism for developing insulin resistance has been modeled in cells  in insulin resistance and non-alcoholic fatty liver disease (NAFLD) in children. Modern dietary habits, rich in omega-6 polyunsaturated fatty acids (n-6 PUFA) and low in n-3 PUFA, are the main reason for intrahepatic fat accumulation that is often preceded by insulin resistance , suggesting that upregulation of FA oxidation during ischemia-reperfusion is cardioprotective. Importantly PPARB/d activation also induces NFR2/PGC1α and antioxidant pathways suggesting a broader role for the regulation of lipid homeostasis. Future studies should address remaining questions that include investigating a direct link between lipid availability on mitochondrial structure, a detailed examination of mitochondrial integrity such as the membrane composition, cristae structures, and formation of respiratory supercomplexes, and how different lipids affect mitochondrial functionality under physiological and stress conditions.Efficient FA oxidation is key to maintaining lipid homeostasis in the cells, and this may be especially important under stress conditions, like limited oxygen during ischemia . PeroxisNKJ, NB and MM-K conceived the original draft, wrote the original manuscript and edited final manuscript. All authors contributed to the article and approved the submitted version.


Rapid diagnostic testing may support improved treatment of COVID patients. Understanding COVID testing and care pathways is important for assessing the impact and cost-effectiveness of testing in the real world, yet there is limited information on these pathways in low-and-middle income countries (LMICs). We therefore undertook an expert consultation to better understand testing policies and practices, clinical screening, the profile of patients seeking testing or care, linkage to care after testing, treatment, lessons learnt and expected changes in 2023.We organized a qualitative consultation with ten experts from seven LMICs  identified through purposive sampling. We conducted structured interviews during six regional consultations, and undertook a thematic analysis of responses.Participants reported that, after initial efforts to scale-up testing, the policy priority given to COVID testing has declined. Comorbidities putting patients at heightened risk  mainly relied on self-identification. The decision to test following clinical screening was highly context-/location-specific, often dictated by local epidemiology and test availability. When rapid diagnostic tests were available, public sector healthcare providers tended to rely on them for diagnosis , while private sector providers predominantly used polymerase chain reaction (PCR) tests. Positive test results were generally taken at ‘face value’ by clinicians, although negative tests with a high index of suspicion may be confirmed with PCR. However, even with a positive result, patients were not always linked to care in a timely manner because of reluctance to receiving care or delays in returning to care centres upon clinical deterioration. Countries often lacked multiple components of the range of therapeutics advised in WHO guidelines: notably so for oral antivirals designed for high-risk mild patients. Severely ill patients mostly received corticosteroids and, in higher-resourced settings, tocilizumab.Testing does not always prompt enhanced care, due to reluctance on the part of patients and limited therapeutic availability within clinical settings. Any analysis of the impact or cost-effectiveness of testing policies post pandemic needs to either consider investment in optimal treatment pathways or constrain estimates of benefits based on actual practice.The online version contains supplementary material available at 10.1186/s12913-023-10305-0. The COVID pandemic has led to a large global disease burden and disruption to economic life since the emergence of SARS-CoV-2 in late 2019. More recently, the disease impact has receded as a result of both natural and vaccine-derived population immunity, leading to the declaration by the World Health Organization (WHO) of the end of the emergency phase of the pandemic on 5 May 2023 [Rapid diagnostic tests (RDTs) have played an important role during the emergency phase of the pandemic as they were used to identify infected people and reduce their contacts with others. During that period, guidance and strategies on RDT use were released by countries and institutions including WHO , 3, AfriWe recruited experts from three world regions  using purposive sampling. Participants were selected by asking collaborators involved in COVID-19 research in these regions to identify suitable candidates or recommend people who could identify them, prioritizing diversity in regions, country income levels, and past COVID-19 burden. We asked for experts with a good knowledge of COVID testing and care pathways in their countries, preferably at the community level. Initially, 11 experts from eight countries were recruited, but one had to withdraw before the start of the study. Hence, the final sample included ten participants from seven countries . The countries span a large range of income levels  and pandemic . Total reported deaths were highest in India, Peru and Indonesia, with South Africa having the highest reported mortality burden in Africa, by far. By inhabitant, Peru had the highest reported and estimated deaths and Nigeria the lowest (more than 10 times fewer deaths per inhabitants). Estimated infections (which may or may not have been symptomatic) were more similar across contexts (Table Testing policies and practices (for both self- and clinician-administered tests);Clinical screening practices, the profile of patients seeking testing/care, and any patient groups likely to be missed;Linkage to care after testing;Treatment/care;Expected future changes and lessons learnt.The ten experts worked for local research institutes, universities, international donors, non-governmental organization partners and/or local hospitals. Five reported having supported their government’s COVID response in an advisory capacity or by contributing to developing guidance Table . We obtaDiscussions used online semi-structured interviews with regional expert groups to account for the practical constraints associated with time zones. There were two meetings with each region over Feb.-Mar. 2023, each taking around an hour and a half, with email follow-up for clarification when needed. A final joint meeting with all regions allowed for presentation of the overall consultation results. The experts also contributed to the drafting of the present paper, of which they are co-authors.The consultations were recorded and transcribed. The results were then analysed through thematic analysis . The theResults are summarised in Table Participants reported that COVID was no longer a policy priority in six of the seven represented countries, mostly because of low disease burden and/or public attention. Once RDTs became available, the public sector tended to rely on them (six countries), although PCR was also sometimes used . Public healthcare providers in two African countries faced persisting difficulties accessing tests, leading to a predominance of clinical assessment over RDTs in those countries. The private sector, when mentioned (which was the case for three of the four participating African countries), was reported to predominantly use PCR testing.In discussing the availability and scale-up of PCR, clinician-administered RDT and self-testing in their countries, most experts  flagged challenges they face or faced. These include a reluctance to approve self-testing and  rapid-testing in the face of a lack of consistent evidence and messaging at the global level, gaps between policies and community implementation, slow facility accreditation for PCR testing, unaccredited facilities providing inaccurate test results, and treatment capacity and funding sustainability Table . These cWhen testing was undertaken, a positive clinician-administered RDT (at least from an accredited facility) was taken as a true positive  and retesting was not conducted. Negative results, however, may be confirmed, generally with PCR , particularly if there was high clinical suspicion of COVID-19 or clinical deterioration to severe illness. Four countries  still did not have a fully implemented self-testing policy, but respondents reported that self-test kits were often available for direct purchase by patients in some form, either in pharmacies, other stores or online.Participants reported that the most common alternative diagnoses for patients presenting with COVID-like symptoms were influenza (mentioned in four countries), malaria (three countries), tuberculosis or respiratory syncytial virus (two countries each). Participants from two countries highlighted insufficient diagnosis of other infections. Certain diseases were commonly mentioned by participants , while others had a strong geographical distribution .We proposed figures of 55–75% sensitivity and 60–90% specificity for clinical assessment of symptomatic cases as a starting point for discussion. Among participants that fed back on these figures, no major trend  was discernible, but the range of plausible values is likely broader  and fears of acquiring infection or lack of trust in the healthcare system were considered to drive this under-representation. Policies of full isolation of patients and not returning the bodies of patients who had died to families have sometimes heightened the reluctance to present to hospitals.We discussed linkage to care (including monitoring systems and patients’ care-seeking behaviours) for patients who self-test and those who have been tested by a clinician, sent home because they had mild illness, then worsened at home. All countries have established rules for monitoring tested patients that are sent home, and four countries  have established systems such as helplines, virtual hospitals and telemedicine systems (at least in part of the country) to support patients. However, the capacity to effectively monitor patients often appeared insufficient and patients themselves were sometimes reluctant to seek care when they worsened Table , a problMild, low-risk positive patients were most likely to be prescribed drugs to alleviate symptoms, and may also self-medicate with antibiotics, drugs for symptoms, home remedies and vitamins. There was limited difference in doctors’ treatment for mild-low risk patients that tested positive vs. negative, relating mostly to antibiotic use. Oral antiviral use was still not widespread, particularly in Africa, hence six of seven countries reported no or very limited difference in the treatment of low and high-risk patients.Severe/critical patients may be given oxygen or mechanical ventilation though availability was still constrained in some cases, particularly in the public sector, as reported by one African participant. Corticosteroids were also given in all surveyed countries , while tocilizumab was only mentioned as being used for severe patient treatment in three countries , with one noting limited availability. A test-negative patient with symptoms strongly indicative of COVID would still be treated as a COVID patient in five countries , at least in terms of corticosteroid initiation, while waiting for confirmatory test results.One of the key possible impacts of testing relates to antibiotic use, which in most countries were often taken by both test-positive and test-negative patients. Overall, participants considered that antibiotics would be used more in test-negative patients, or had no clear answer.Two countries  expected to get expanded access to COVID antivirals. Meanwhile, self-tests may become more readily available in one of the African countries participating in this study. New initiatives include the development of a pandemic preparedness programme and of a network of centres to test for multiple respiratory infections. One participant also expressed the wish to monitor long-COVID, while noting the limited capacity for that purpose, and another highlighted the need to develop home management standards, including around the use of corticosteroids, for people who refuse hospitalization.Some lessons learnt include how development of in-house reagents has lowered costs in one country. Finally, one participant expressed the concern that WHO’s declaration that COVID-19 is no longer a public health emergency may negatively affect costs and licensing approval processes.The main findings of these expert discussions were to give important insights on the realities of COVID testing and care pathways in LMICs, with relevance to cost-effectiveness analysis and future pandemic preparedness. Experts reported that RDTs were often employed in settings where COVID tests were available, but that the choice of which patients were tested was highly context-specific reflecting local epidemiology, perceived morbidity and/or test availability. Experts from African countries reported less use of PCR overall in the public sector than those from Asian/Latin American countries, plausibly a reflection of lower national income and pandemic priority on average. Doctors were reported to have ignored other diseases, such as tuberculosis, at the height of COVID, and were sometimes ignoring COVID now that the peak of the pandemic had passed. Similarly to experiences with other rapid tests , 12, chaEvaluation of different COVID testing strategies should be based on understanding of conditions in the local context, considering treatment availability, risk identification, and monitoring systems, rather than assuming testing alone will improve outcomes. Guidelines should address the appropriateness of testing if limited or no treatment is available. Further, like with other diseases , testingAs with other RDTs , 19, patFinally, our results illustrate the extent to which efforts to scale-up COVID testing faced and will continue to face major challenges, ranging from a lack of scientific consensus to administrative and funding challenges or healthcare staff reluctance. This highlights the need for advanced preparedness and protocols to enable smooth approval and implementation of diagnostic policies during pandemics.One limitation of this work is our small sample size (ten respondents from seven countries), although we included respondents from countries in a range of geographical regions, income levels and pandemic severity to ensure maximum variety in participants. Hence, the results should be interpreted as providing general insights rather than precise figures, particularly so when comparing regional groupings. Furthermore, not all participants had expertise or direct experience of all issues being discussed. While some countries had two participants with complementary profiles to provide better insights, answers may still not always reflect the entire range of contexts  found within each country. We also cannot exclude some desirability bias, as experts may have sometimes been tempted to report on ideal behaviours instead of actual practices, though the many challenges they flagged suggests this bias may not have been widespread. Finally, this consultation was an opportunity for participants to provide some insights as to historical successes and challenges in their countries. However, most of the discussion focused on the present time, meaning that the practices discussed generally reflect the situation in early 2023 rather than throughout the pandemic.Our findings have important implications for future research, in particular cost-effectiveness analyses, and are already being used to inform a decision analytic model comparing different COVID testing options for severe cases in LMICs, given countries’ specific screening and testing practices and treatment capacities. Our results highlight obstacles that could reduce the cost-effectiveness of COVID testing in some LMICs, including insufficient availability of key therapeutics, limitations of relying on self-reporting of risk status and suboptimal care-seeking. Complementary, context-specific research  is important. From a policy perspective, our findings suggest that COVID testing needs to be accompanied by investment in comprehensive packages to ensure testing is associated with optimal care pathways.Additional file 1.


Diagnosing most cancers at an earlier stage improves outcomes because treatments are more effective and often less invasive. This study looked at the health patterns of adults enrolled in Alberta’s Tomorrow Project before they were diagnosed with cancer to identify factors related to cancers that are caught early or late. These identified factors were then tested in a similar group of adults from the British Columbia Generations Project who also subsequently developed cancer, to see how well they could predict stage at diagnosis. The confirmed health patterns can be used to improve cancer prevention programs and activities to find cancer earlier in people who are at most risk of being diagnosed with late-stage cancer.Risk prediction models for cancer stage at diagnosis may identify individuals at higher risk of late-stage cancer diagnoses. Partial proportional odds risk prediction models for cancer stage at diagnosis for males and females were developed using data from Alberta’s Tomorrow Project (ATP). Prediction models were validated on the British Columbia Generations Project (BCGP) cohort using discrimination and calibration measures. Among ATP males, older age at diagnosis was associated with an earlier stage at diagnosis, while full- or part-time employment, prostate-specific antigen testing, and former/current smoking were associated with a later stage at diagnosis. Among ATP females, mammogram and sigmoidoscopy or colonoscopy were associated with an earlier stage at diagnosis, while older age at diagnosis, number of pregnancies, and hysterectomy were associated with a later stage at diagnosis. On external validation, discrimination results were poor for both males and females while calibration results indicated that the models did not over- or under-fit to derivation data or over- or under-predict risk. Multiple factors associated with cancer stage at diagnosis were identified among ATP participants. While the prediction model calibration was acceptable, discrimination was poor when applied to BCGP data. Updating our models with additional predictors may help improve predictive performance. Cancer is the leading cause of morbidity and mortality in Canada, with an estimated two in five Canadians expected to develop cancer in their lifetime and one in four Canadians expected to die from the disease . Cancer Cancer stage at diagnosis is an important determinant of cancer survival . IndividCancer screening programs can help identify cancer in its early stages, thus enabling curative treatment and enhancing survival . HoweverRisk prediction models are increasingly used to support clinical decision-making . While aThis feasibility study aimed to develop sex-specific partial proportional odds risk prediction models to identify shared risk factors associated with cancer stage at diagnosis for all cancer types using data from a large population-level prospective cohort study in Alberta, Canada. Prediction models were externally validated on a population-level cohort in British Columbia (BC), Canada.We used data from two prospective cohorts to develop and externally validate risk prediction models for cancer stage at diagnosis. Both cohorts contributed to the Canadian Partnership for Tomorrow’s Health (CanPath), a pan-Canadian prospective cohort that has collected genetic, clinical, behavioral, and environmental data to support research on cancer and other chronic diseases .n = 26,554) [Models were developed using data from Alberta’s Tomorrow Project (ATP). From 2000 to 2015, 55,000 adults living in Alberta, Canada aged 35–69 years with no reported history of cancer (excluding non-melanoma skin cancer) were enrolled in ATP ,33. The  26,554) ,33. The  26,554) . ATP par 26,554) ; howeverExternal validation was performed using data from the BCGP. From 2009 to 2016, nearly 30,000 adults between the ages of 35 and 69 years living in BC, Canada, were enrolled in the BCGP . Data weThis study included all incident cancers (excluding non-melanoma skin cancer) diagnosed from the year of cohort enrollment to January 2018 (ATP) and January 2021 (BCGP). Due to the small number of some cancer types, all cancers were combined to identify shared risk factors associated with cancer stage at diagnosis. Cancer stage at diagnosis was defined according to the Tumor, Node, Metastasis staging system, whereby cancers are staged from stage I  to IV (cancer has metastasized) . Cancer Candidate predictors associated with cancer stage at diagnosis were selected based on evidence from the literature and were subsequently limited to those that were available in both ATP and BCGP cohorts . Due to Preliminary analyses have been described elsewhere ,8,9 but p < 0.15) were subsequently considered for stepwise variable selection. Stepwise selection was adopted, with the proportionality assumption and interactions assessed at each step. A significance level of p < 0.05 was used to determine which variables remained in the final model. The influence of outliers was investigated by computing the differences in effect and fit  per participant. Model checking included goodness-of-fit tests, indices of model performance, and diagnostics for binary logistic regression per dichotomization of stage at diagnosis owing to the shortage of available PPO model checking methods. All analyses were performed using R  and SAS software .Associations between predictor variables and cancer stage at diagnosis among ATP participants were modelled using partial-proportional odds (PPO) models. Owing to the presence of sex-specific cancer types, separate analyses were conducted for males and females. Proportional and partial-proportional univariable screening was performed to assess the association of each variable with cancer stage. Variables that passed univariable screening (Discrimination (ability to distinguish between outcomes) and calibration (accuracy of risk predictions) of the ATP-derived PPO models were evaluated among male and female BCGP participants. Discrimination was assessed using the ordinal concordance statistic (ORC) . The ORCIn total, 2227 and 1845 incident cancers were identified in the ATP and BCGP cohorts, respectively. We excluded 555 ATP and 990 BCGP participants with missing cancer staging data . Other cOur study included 2112 participants  who developed cancer until January 2018 . Among mThe results of the final sex-specific PPO models are summarized in Among females, having a mammogram or a sigmoidoscopy or colonoscopy was associated with an earlier stage at diagnosis . Older age was associated with a later stage at diagnosis when comparing stages III and IV with stages I and II . Reproductive health factors, including a greater number of pregnancies and history of hysterectomy, were associated with a later-stage diagnosis .A total of 855  BCGP participants who developed cancer between 2009 and 2021 were included in the study . DiffereThe performance of the risk prediction models differed according to sex . When apIn this feasibility study, we developed and externally validated sex-specific PPO models that identified sociodemographic and health-related factors associated with cancer stage at diagnosis. Prediction models for both males and females showed low discriminative performance in distinguishing between stages at diagnosis. Calibration was better in males than in females.Our risk prediction models analyzed data from male and female ATP participants. Among males, former or current smoking was associated with late-stage cancer diagnosis, while older age at diagnosis, full- or part-time employment, and history of PSA testing were associated with earlier cancer stage at diagnosis. Among females, a history of mammography, sigmoidoscopy, or colonoscopy was associated with earlier-stage diagnoses, whereas older age at diagnosis, a greater number of pregnancies, and a history of hysterectomy were associated with late-stage cancer diagnosis. Our findings are consistent with some, but not all, previous studies. For instance, smoking has previously been identified as a risk factor for advanced-stage cancer in some studies ,13, withWe externally validated our prediction models by examining model discrimination and calibration (mean and weak). Our models showed poor discrimination, with ORCs for males and females near 0.5, indicating that the model’s ability to separate outcomes in the validation data was similar to that of a random model . The calThe development of ordinal risk prediction models for cancer outcomes is novel and, to our knowledge, only one has been previously developed to predict cancer stage at diagnosis ,24. The Our prediction models are the first to our knowledge to apply cancer stage at diagnosis as an ordinal outcome for all cancers using novel statistical methods ,40,42. MThis study has some limitations. First, there were insufficient data to explore individual cancer types separately. Validation results for separate PPO models for breast cancer , prostate cancer , and lung plus colorectal cancer had very poor discrimination and calibration (results available from corresponding author upon request). Thus, all cancers were pooled. Many cancers have distinct risk factors; therefore, creating sex-specific models to predict stage at diagnosis across all cancer types may have reduced our models’ predictive performance. However, most cancers also have shared risk factors ,29, whicWith ongoing data harmonization across cohorts within CanPath , our preWe developed and externally validated sex-specific PPO models to predict factors associated with cancer stage at diagnosis among ATP participants. We identified several sociodemographic and health-related risk factors associated with stage at diagnosis for all cancer types among males and females. External validation of our models showed poor discrimination and meanly and weakly calibrated risk predictions. Updating our models with additional predictors and ongoing external validation in other cohorts may help improve predictive performance, as our study found that it is feasible to do so. Prediction models that identify risk factors associated with cancer stage at diagnosis can help identify individuals at a higher risk of developing late-stage cancer, and thus greatly improve cancer survival. Further research is required to develop more robust prediction models.