Transmission of drug-resistant tuberculosis (DR-TB) is ongoing. Finding individuals with DR-TB and initiating treatment as early as possible is important to improve patient clinical outcomes and to break the chain of transmission to control the pandemic. To our knowledge systematic reviews assessing effectiveness, cost-effectiveness, acceptability, and feasibility of different case-finding strategies for DR-TB to inform research, policy, and practice have not been conducted, and it is unknown whether enough research exists to conduct such reviews. It is unknown whether case-finding strategies are similar for DR-TB and drug-susceptible TB and whether we can draw on findings from drug-susceptible reviews to inform decisions on case-finding strategies for DR-TB.This protocol aims to describe the available literature on case-finding for DR-TB and to describe case-finding strategies.We will screen systematic reviews, trials, qualitative studies, diagnostic test accuracy studies, and other primary research that specifically sought to improve DR-TB case detection. We will exclude studies that invited individuals seeking care for TB symptoms, those including individuals already diagnosed with TB, or laboratory-based studies. We will search the academic databases including MEDLINE, Embase, The Cochrane Library, Africa-Wide Information, CINAHL, Epistemonikos, and PROSPERO with no language or date restrictions. We will screen titles, abstracts, and full-text articles in duplicate. Data extraction and analyses will be performed using Excel (Microsoft Corp).We will provide a narrative report with supporting figures or tables to summarize the data. A systems-based logic model, developed from a synthesis of case-finding strategies for drug-susceptible TB, will be used as a framework to describe different strategies, resulting pathways, and enhancements of pathways. The search will be conducted at the end of 2021. Title and abstract screening, full text screening, and data extraction will be undertaken from January to June 2022. Thereafter, analysis will be conducted, and results compiled.This scoping review will chart existing literature on case-finding for DR-TB—this will help determine whether primary studies on effectiveness, cost-effectiveness, acceptability, and feasibility of different case-finding strategies for DR-TB exist and will help formulate potential questions for a systematic review. We will also describe case-finding strategies for DR-TB and how they fit into a model of case-finding pathways for drug-susceptible TB. This review has some limitations. One limitation is the diverse, inconsistent use of intervention terminology within the literature, which may result in missing relevant studies. Poor reporting of intervention strategies may also cause misunderstanding and misclassification of interventions. Lastly, case-finding strategies for DR-TB may not fit into a model developed from strategies for drug-susceptible TB. Nevertheless, such a situation will provide an opportunity to refine the model for future research. The review will guide further research to inform decisions on case-finding policies and practices for DR-TB.DERR1-10.2196/40009 Mycobacterium tuberculosis strains resistant to first-line antituberculosis drugs, strategies to control tuberculosis (TB) became even more challenging [With the emergence of llenging . It is ellenging . Althougllenging .Finding individuals with DR-TB and initiating treatment as early as possible is important to improve patient clinical outcomes and to break the chain of transmission to help control the pandemic. But despite new diagnostic technologies, only 38% of the estimated number of people who developed DR-TB initiated treatment in 2019 [TB can be detected after an individual presents passively to health services or through one of several different screening pathways depending on the case-finding strategy of a TB program . PathwayTo our knowledge, systematic reviews assessing effectiveness, cost-effectiveness, acceptability, and feasibility of different case-finding strategies for DR-TB to inform research, policy, and practice have not been conducted, and it is unknown whether enough research exists to conduct such reviews. It is also unknown whether case-finding strategies are similar for DR-TB and drug-susceptible TB and whether we can draw on findings from reviews on drug-susceptible TB to inform decisions on case-finding strategies for DR-TB.We therefore aim to conduct a scoping review to chart existing literature on case finding for DR-TB and identify priority questions for a systematic review ,8. We wiThe Arksey and O’Malley framework ,10, the The question for our review is as follows: what literature is available on case-finding for DR-TB and which case-finding strategies are described? We will screen studies that have sought to improve case detection for DR-TB.With assistance from an information specialist, we will search MEDLINE (PubMed), Embase (Ovid), and The Cochrane Library because they are top academic databases for biomedical research, medicine, and health care; Africa-Wide Information (EBSCOhost) owing to the high prevalence of TB in sub-Saharan Africa; CINAHL (EBSCOhost) because nurses and allied health staff are often the ones carrying out the actual case-finding; and Epistemonikos and PROSPERO to complement the search for systematic reviews. To obtain the highest possible yield, we will use no language or date restrictions; however, if we are not able to translate the articles, we will report them under excluded articles with reasons for exclusion. Reference lists of included studies will be searched.The preliminary search string will include combinations of the following 3 domains: terms related to “tuberculosis,” terms related to “drug resistance,” and terms related to “case finding,” “case detection,” “screening,” “contact investigation,” and “contact tracing.”Appropriate MeSH  terms will be added to the different databases. Search strategies from each electronic database are detailed in We will use Rayyan systematic review software  to screeWe will develop a data extraction form in Excel (Microsoft Corp). The data extraction form will be applied to all primary research reports to collect standard information on each study. Information will include the following: authors, journal name, and year of publication; aim or purpose of the research; study design; country characteristics ; participants’ characteristics ; target group and how the group was identified, if applicable; interventions ; treatment support, including preventive therapy; and outcomes assessed.Five authors  will extract the data (1 author per paper). A second reviewer (SvW or MC) will check extracted data from each study. The data extraction team and other coauthors will meet regularly after each round of screening of 5-10 studies to determine whether their approach is consistent and in line with the research question.This paper describes the protocol for a scoping review; hence, we did not deem it appropriate to involve patients or the public in the design, conduct, reporting, or dissemination plans of our research.We will provide a narrative report with supporting figures or tables to summarize the data. Definitions used in the scoping review:Drug-resistant tuberculosis (TB): all types of drug-resistant TB, including single drug–resistant TB, multidrug-resistant TB, extensively drug-resistant TB, and any other drug-resistant TB reported by the authors.Systematic screening for active TB: “The systematic identification of people with suspected (presumptive) active TB, in a predetermined target group, using tests, examinations or other procedures that can be applied rapidly. Among those screened positive, the diagnosis needs to be established by one or several diagnostic tests and additional clinical assessments, which together have high accuracy” [ccuracy” .A screening tool: tests, examinations, or other procedures used for systematic screening for active TB. Examples of TB screening tools include a structured symptom-based questionnaire, chest radiography, or an algorithm [lgorithm . AlgoritA diagnostic tool: tests, examinations, or other procedures used to establish a diagnosis of TB in people identified with presumptive TB. Examples of TB diagnostic tools include a clinical algorithm, sputum smear microscopy, the Xpert MTB/RIF test, or cultures [cultures .TB symptoms: any TB symptom, including cough, fever, night sweats, weight loss, or a combination of TB symptoms as defined by the study authors.Care seeking: people seeking care for a perceived health problem.TB care seeking: people seeking care specifically for TB symptoms.A risk group: any group of people in whom the prevalence or incidence of TB is significantly higher than that in the general population. Examples of risk groups include a whole population within a geographical area or TB contacts [contacts .A clinical risk group: individuals diagnosed with a specific disease or condition that increases their risk for TB; for example, people living with HIV.Presumptive TB: presumptive TB is identified when a provider identifies a patient with suspected active TB. In the context of screening, a person who screens positive is a presumptive TB case.Passive case finding, passive case finding with an element of systematic screening, triage, enhanced case finding, active case finding, contact tracing or contact investigation, and intensified case finding: some of these definitions overlap and are used inconsistently within the literature. We will therefore use our logic model (ic model  to clearA systems-based logic model developed from a synthesis of case-finding strategies for drug-susceptible TB  will be Quality appraisal will not be conducted because this is a scoping review and our interest is in the existing evidence base, regardless of study design and quality.The search will be conducted at the end of 2021. Title and abstract screening, full text screening, and data extraction will be carried out from January to June 2022. Thereafter, analysis will be conducted and results written up.This scoping review will chart existing literature on case finding for DR-TB; this will help us determine whether primary studies on effectiveness, cost-effectiveness, acceptability, and feasibility of different DR-TB case-finding strategies exist. This will assist us in formulating potential questions for a systematic review. We will also describe case-finding strategies for DR-TB and how they fit into a model of case-finding strategies for drug-susceptible TB.Our multidisciplinary review team consists of researchers with extensive experience in TB-related research and the conduct of systematic reviews and qualitative evidence synthesis. Their experience would be invaluable in collating and summarizing diverse literature in a sensible way. Another strength of our review is the use of a systems-based logic model that was developed from a synthesis of case-finding strategies for drug-susceptible TB. The model will help construct meaningful pathway descriptions for possible comparisons in future research and to assess whether case-finding pathways for DR-TB are similar to those for drug-susceptible TB.One limitation to the review is the diverse, inconsistent use of intervention terminology within the literature, which may result in missing relevant studies. Although we cannot completely overcome this problem, we will work with an information specialist to pilot and optimize our search strategy, and we will discuss potential refinements to our search at regular meetings during the screening phase. Poor reporting of intervention strategies may also cause misunderstanding and misclassification of interventions. However, we do not assess effectiveness as an outcome; therefore, bias due to misclassification would be a minor issue. Lastly, case-finding strategies for DR-TB may not fit into a model developed from those for drug-susceptible TB. Nevertheless, such a situation will provide an opportunity to refine the model for future research.This scoping review will chart the existing body of literature on case-finding strategies for DR-TB and will guide further research to inform decisions regarding case-finding policies and practices for DR-TB.


The Seymour fracture is a juxta-epiphyseal fracture of the terminal phalanx of the finger. Sources vary on the recommended management, with some advocating treatment without K-wires to avoid metalwork-associated infection, and others suggesting that K-wire fixation is necessary due to the risks of fracture re-displacement.A best evidence topic in paediatric hand surgery was written according to a structured protocol. Searches were performed on December 28, 2021 in Cochrane library and PubMed.69 papers were found using the reported search strategy, and eight papers representing the best evidence to answer this question are discussed.The evidence on this subject is suboptimal as five of these studies were case-series that do not make direct comparisons between the question's intervention and control groups, and the other three were single-centre retrospective cohort studies with no randomisation.The best evidence topic concludes that K-wire fixation appears to be associated with a higher rate of physeal disturbance and lower rates of infection, fracture re-displacement, and flexion deformity. •K-wire fixation appears to be associated with higher rates of physeal disturbance.•And with lower rates of infection, fracture re-displacement, and flexion deformity.•Most will have normal clinical and radiographic findings at long-term follow-up. The distal interphalangeal joint appears to be in slight flexion at rest, the nail plate appears longer than those of the other fingers with signs of bleeding from the nailbed, and plain films demonstrate a physeal fracture of the distal phalanx with volar angulation. The diagnosis of a Seymour fracture is made. A colleague comments that K-wire fixation is typically required but some elect to manage the fracture conservatively. You wonder what the effect of K-wire fixation is on patient outcomes.3In children with a Seymour fracture (patient), does K-wire fixation (intervention) compared with no K-wire fixation (comparison) influence clinical findings, radiographic findings, and complication rates (outcomes)?4Searches were all performed on December 28, 2021.4.1Search [All Text]: ((seymour* AND fracture*) OR )) AND (K-wir* OR Kirschner OR wir* OR fixat* OR pin*).4.2Search: ((seymour*[Title/Abstract] AND fracture*[Title/Abstract]) OR )) AND (K-wir*[Title/Abstract] OR Kirschner*[Title/Abstract] OR wir*[Title/Abstract] OR fixat*[Title/Abstract] OR pin*[Title/Abstract]). Filter applied: Humans.In addition, the reference lists of the relevant papers were searched.5Search results: 69 references, seven relevant to the question. One further relevant reference identified as a secondary reference.6The results of the eight papers are summarised in 7Long-term outcomes were favourable regardless of treatment modality . Where mThere are three main limitations to the above studies. First, five of the studies are case-series that do not make direct comparisons between those treated initially with K-wires and those who were not. Second, in the studies where such comparisons were made there was a paucity of statistical analyses. Finally, in the study where statistical analyses were performed, this was a single-centre retrospective cohort study that did not control for factors such as severity of initial injury, administration of antibiotics, wound debridement, nor nailbed suture, all of which may have influenced outcomes. Therefore, further research for Seymour fracture management is needed in the form of a randomised controlled trial, to confirm or refute the above findings. This will likely need to be multi-centre in view of the relatively infrequent presentation of Seymour fractures . Such a 8Most patients will have normal clinical and radiographic findings at long-term follow-up regardless of treatment modality. K-wire fixation appears to be associated with a higher rate of physeal disturbance in children with a Seymour fracture. K-wire fixation appears to be associated with lower rates of infection, fracture re-displacement, and flexion deformity. There is a need for large-scale randomised controlled trials in Seymour fractures that do not demonstrate instability after open reduction to determine the treatment modality with better patient outcomes.Ethical approval was not required for this study.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Riki Houlden devised the question, performed the literature search, appraised the papers, tabulated the results, and wrote the manuscript. He submitted and gave final approval of the version to be published.1.Name of the registry: not applicable2.Unique Identifying number or registration ID: not applicable3.Hyperlink to your specific registration (must be publicly accessible and will be checked): not applicableRiki Houlden.Not applicable.The author has no conflicts of interest to declare.


Optimism, burnoutand secondary traumatic stress, but not coping strategies,self-efficacy, compassion satisfaction, or self-compassion, mediatedboth the relationship between pre-pandemic stress and resilience andCOVID-19 stress and resilience. Increased job demands caused by thepandemic, the nature and duration of COVID-19 stress may explain thisfinding. Training and supervision practices can help MHPPs deal withjob demands under circumstances of general and extreme stress.Utilising an online survey, this study aimed to investigate theconcurrent effects of pre-pandemic and COVID-19 stress on resiliencein Mental Health Psychology Practitioners (MHPPs)( Although the erroneous belief that Mental Health Psychology Practitioners (MHPPs)should not be affected by their work has prevailed for years , researcA pandemic like COVID-19 is considered among situations that may lead to collectivetrauma – the psychological upheaval that is shared by a group of people who allexperience an event . CollectIt is likely that in such situations MHPPs are expected to demonstrate competencieslike integrity and, above all, resilience. Resilience is a dynamic, interactiveprocess which is defined in terms of successful adaptation to the environment inthe face of major threat, traumatic experiences or severe adversity . IninveFurthermore, the present study adopted the transactional theory of stress , which dRooted in the above transactional theory, the job demand resource model  divides Drawing on these theories, the individual factors of self-efficacy and optimism areexplored below, especially in relation to how they might link to the ways stress(both pre-pandemic and COVID-19 stress) influences the development of resiliencein individuals.The relationship between self-efficacy and stress has been widely investigated,with various studies reporting a negative correlation between high generalself-efficacy and stress and anxiety . TheundMoreover, self-efficacy can be developed through experiences of mastery and theanticipation of competent performance .Thus, wOptimism, the belief that future events will have positive outcomes, has beenwidely linked to positive outcomes  and has Considering the nature of MHPPs’ work and the fact that resilience arises fromthe operation of adaptational systems, we tested the mediating role ofcoping strategies in the relationship between stress and resilience.focus of coping strategies, categorising them intoapproach and avoidant strategies  and in coping with job-related stress in therelationship between pre-pandemic perceived stress andresilience and COVID-19 stress and resilience.The inclusion of these specific individual features was informed by thefindings of semi-structured interviews with MHPPs conducted before thecurrent investigation, which revealed that personal qualities assisted theseprofessionals in coping with stress and demonstrating resilience. In oureffort to understand the relationship between stress and resilience inMHPPs, we focussed on the individual characteristics of self-efficacy andoptimism. These are strongly linked to cognitive appraisals, namely theindividual’s ability to appraise a stressor as threatening ornon-threatening, and decide whether they have the resources to cope with thestressor in an effective way .MoreoveIn line with the transactional model of stress  andthe Undoubtedly, COVID-19 changed the nature of MHPPs’ job. Face to face therapysessions were replaced by tele-therapy, access to resources became limited,whilst their clients experienced additional distress and mental healthissues. These changes, the increased workload and job demands, which oftenlead to experiences of secondary traumatisation, have affected MHPPswellbeing in a negative manner.We also hypothesised that the relationship between COVID-19 stress andresilience will be mediated by fewer factors in comparison to therelationship between pre-pandemic stress and resilience. This assumption wasbased on the nature and duration of stress caused by COVID-19, which iscertainly different than stress experienced prior the pandemic. Arguably,the pandemic-related stress differed in terms of controllability andpredictability from the stress experienced prior to the pandemic; thesecharacteristics can determine not only the effects of stress, but also howstress is explained . In termTo conclude, gaining insight into the experiences of MHPPs during this complexhistorical time holds the potential to assist in the development ofprogrammes, policies and practices which can support this population indealing with any additional stressors their role entails. In turn, this canpotentially contribute to increased motivation, empowerment and personalfulfilment, leading to more positive outcomes for the service users. was determined using power analysis based on Cohen’s technique during the firstlockdown in the UK. The link to our anonymous online survey wasadvertised via social media and professional bodies.Pre-pandemicPerceived Stress was measured retrospectively with a10-item self-report questionnaire . Inour sample internal consistency was 0.85.The 10-item Revised Life Orientation Test LOT-R;  wasutilSelf-Efficacy was assessed with the 10-item GeneralisedSelf-Efficacy (GSE) measure .M = 53.17; SD = 11.53). Aboutone third of the sample  had aMaster’s degree and the years of their work experience as a mentalhealth psychology practitioners ranged from 0.1 to 50. Themajority of participants were self-employed , worked in private practice  and were in personal psychotherapy orprofessional supervision . As far astheir personal situation was concerned, at the time of data collectionmost of respondents  were in arelationship  and livedwith one person . Furthermore, mostof our participants  lived with nochildren during the lockdown, and only 65 (20.00%) of them reportedhaving other caring duties such as looking after older parents .Our sample consisted mainly of females (80.62%), aged 25–79 years, optimism(LOT), approach (AP) and avoidant (AV) coping strategies,self-compassion (SC), compassion satisfaction (CS), burnout (BU) andsecondary traumatic stress (STS), in the relationship betweenpre-pandemic stress (PSS) and COVID-19 stress (RSQ) and resilience(RES). All calculations were performed in JASP software version 0.13.1.2r = −0.03,BF10 = 0.08, 95% CI );AP and RSQ , RSQand CS , AVand CS  . Second, we performed a series ofregressions analyses to test the relationship among the independentvariables, possible mediators and the outcome variable.Prior to testing the mediation effects, we ran a series of analyses todetermine if mediation was appropriate. First, exploratory correlationanalyses indicated medium to strong correlations between all variablesexcluding associations between AP and PSS  = −9.32,p < 0.001; β = −0.26,t(323) = −4.92, p < 0.001). TheBayesian model selection with the JZS priors (BF10 = 3.18e+15) compared to models witheither predictors , explaining 22.4% ofvariance in the resilience scores. The Bayesian model-averagedanalysis showed that a one-unit increase in RSQ added about 0.18 unitsin decreasing resilience. A one-unit increase in PSS added about0.76 units in decreasing resilience. Therefore, this analysis showedthat both PSS and RSQ were associated with resilience scores .Both the PSS and RSQ were associated with the resilience scores. The results of these analyses are summarised in The results in F = 74.98,p < 0.001). The results outcome of thisanalysis are presented in A multiple regression was conducted to test whether the possiblemediators were associated with the resilience scores. Using entermethod it was found that, overall, the mediators accounted for 64.7%of the variance in resilience  were unlikely tomediate the relationship between PSS, RSQ and resilience and thus theywere omitted from the mediation model.Our initial model included PSS and RSQ as independent variables,resilience as an outcome variable and six variables  as mediators. Using parallel mediation, wetested each proposed mediator while accounting for the shared variancebetween them. The path diagram of the mediation model includesThe multiple mediator model was fitted using SEM where residualsassociated with the mediators were permitted to covary. The modelshowed a reasonably good model fit according to multiple SEM fitstatistics and indices (Root Mean Square Error of Approximation(RMSEA) = 0.049, 95% CI ); Comparative fit index(CFI) = 0.993; Tucker-Lewis index (TLI) = 0.977  . The model fit metrics suggestedthat our theoretically motivated model of the covariance amongvariables provides a good approximation of the data obtained in thisstudy.This study investigated the relationship between both pre-pandemic stress andCOVID-19 stress and resilience, and examined the mediation effects ofself-efficacy, optimism, coping strategies, self-compassion and professionalquality of life on the relationship between stress and resilience in MHPPs.Three interesting findings emerged. First, in line with the transactionalmodel of stress  and the Second, consistently with previous findings , it wasThird, COVID-19 stress was not associated with compassion satisfaction. Thismay suggest that unprecedented situations, such as COVID-19, are not usuallylinked to MHPPs’ satisfaction with their abilities to take care of sufferingpatients possibly because of their belief that their work has a certaindegree of social value . HoweverIn the mediation model only indirect effects were significant, suggesting fullmediation. As expected, we found that pre-pandemic stress, in contrast toCOVID-19 stress, was mediated by a wider number of factors. Only threevariables  mediated both the relationship betweenpre-pandemic stress and resilience and the relationship between COVID-19stress and resilience. In other words, while certain individual featuresexplained the effect of perceptions about pre-pandemic stress on resilience,they did not affect the relationship between COVID-19 stress and resilience.We could argue that the nature of the stress generated by the pandemic, incontrast to general pre-pandemic stress, could not be processed through thelens of past experiences ; this maMost importantly, the above finding suggests that optimism, burnout andsecondary traumatic stress represent individual variables crucial tounderstand how MHPPs may be affected by and adapt when exposed to generalstress and to a crisis, such as COVID-19. Therefore, prevention strategiesshould focus on these particular factors.Optimists tend to perceive stressful events as learning opportunities  and inteOn the other hand, our study identified that the two aspects of compassionfatigue, burnout and secondary traumatic stress, are the factors that hinderthe development of resilience in MHPPs when dealing with general stress andexceptionally stressful circumstances such as COVID-19. During the firstlockdown in the UK demands for mental health care increased massively,resulting in higher exposure to trauma and higher requirements for empathy.These are linked to compassion fatigue symptoms in psychotherapists  and consThese findings highlight the importance of training and supervision practicesthat allow MHPPs to reflect on their capacity to deal with their workloadand job demands under circumstances of general and extreme stress. Theseprocedures would assist professionals in identifying early signs of burnoutand secondary traumatic stress . They alThe conclusions of this study should be evaluated in the light of itslimitations. First, although we modelled effects in line with theory andevidence, we assumed a causal path of associations via cross-sectional data.Longitudinal data are needed to exclude other possibilities about thedirection of the identified relations. Second, we solely relied onself-reported data and thus the possibility of common source biases must beacknowledged. Thirdly, our mediation model included only specific individualfactors; future studies would benefit by the inclusion of other individualfactors , and processes found within thefamily system and the community which play a significant role in coping andresilience . MoreoveFuture research should also consider the way that practitioners experiencedonline therapy. With the outbreak of COVID-19 MHPPs experienced a suddentransition from face-to-face to online therapy. Research has explored theconsequences of such a radical change in psychological treatments amongMHPPs; there is evidence that the remote psychological treatment waschallenging for the MHPPs due to the technological and usability problems,lack of technological and logistical support, and difficulties incommunicating and bonding with their clients .AdditioDespite these limitations, however, it is important not to lose sight of thestudy’s strengths. The inclusion of specific individual factors in our modelwas informed by the findings of semi-structured interviews we conductedbefore the present study. Moreover, data collection started in June 2020,when a lockdown was ongoing in the UK and this enabled us to accuratelycapture MHPPs’ experiences. Additionally, this study added to the knowledgeabout the relationship between stress and resilience by highlighting thestrong association among three particular personal factors  and resilience in a group ofprofessionals that played and continues to play a significant role infighting off the negative effects of COVID-19.Finally, when contrasting the effects of optimism, burnout and STS we foundstronger mediating effects of optimism and burnout for the relationshipbetween pre-pandemic stress and resilience compared to the relationshipbetween COVID-19 stress and resilience. COVID-19 is most likely notexperienced in the same way as general, pre-pandemic stress because it ischaracterised by a cumulation of stress-linked repercussions and its effect,according to the allostatic load model , can oveIn conclusion, our research can have widespread implications for preventionstrategies, both within and outside the COVID-19 context. Our findingsdemonstrated that strategies allowing the development of ‘learned optimism’,as well as detecting burnout and STS symptoms, can reduce the detrimentaleffects of stress on MHPPs’ resilience levels. Future research should extendthese findings by exploring time trajectories and investigating the effectof family and social support in the relationship between both general stressand stress related to unprecedented situations and resilience in MHPPs.Click here for additional data file.Supplemental material, sj-docx-1-hpq-10.1177_13591053211059393 forIndividual factors in the relationship between stress and resiliencein mental health psychology practitioners during the COVID-19 pandemicby Constantina Panourgia, Agata Wezyk, Annita Ventouris, AmandaComoretto, Zoe Taylor and Ala Yankouskaya in Journal of HealthPsychologyClick here for additional data file.Supplemental material, sj-docx-2-hpq-10.1177_13591053211059393 forIndividual factors in the relationship between stress and resiliencein mental health psychology practitioners during the COVID-19 pandemicby Constantina Panourgia, Agata Wezyk, Annita Ventouris, AmandaComoretto, Zoe Taylor and Ala Yankouskaya in Journal of HealthPsychologyClick here for additional data file.Supplemental material, sj-html-4-hpq-10.1177_13591053211059393 forIndividual factors in the relationship between stress and resiliencein mental health psychology practitioners during the COVID-19 pandemicby Constantina Panourgia, Agata Wezyk, Annita Ventouris, AmandaComoretto, Zoe Taylor and Ala Yankouskaya in Journal of HealthPsychologyClick here for additional data file.Supplemental material, sj-jasp-3-hpq-10.1177_13591053211059393 forIndividual factors in the relationship between stress and resiliencein mental health psychology practitioners during the COVID-19 pandemicby Constantina Panourgia, Agata Wezyk, Annita Ventouris, AmandaComoretto, Zoe Taylor and Ala Yankouskaya in Journal of HealthPsychologyClick here for additional data file.Supplemental material, sj-pdf-5-hpq-10.1177_13591053211059393 forIndividual factors in the relationship between stress and resiliencein mental health psychology practitioners during the COVID-19 pandemicby Constantina Panourgia, Agata Wezyk, Annita Ventouris, AmandaComoretto, Zoe Taylor and Ala Yankouskaya in Journal of HealthPsychologyClick here for additional data file.Supplemental material, sj-txt-6-hpq-10.1177_13591053211059393 forIndividual factors in the relationship between stress and resiliencein mental health psychology practitioners during the COVID-19 pandemicby Constantina Panourgia, Agata Wezyk, Annita Ventouris, AmandaComoretto, Zoe Taylor and Ala Yankouskaya in Journal of HealthPsychology


ASPSCR1-TFE3 fusion and TMB-H. Following eight months of anlotinib monotherapy, the patient’s disease progressed but continued to benefit from subsequent use of anlotinib combined with toripalimab for 19 months. Another 63 year-old male patient was diagnosed with UPS. PD-L1 was positive and NGS revealed TMB-H. Following 19 months of anlotinib monotherapy, the patient’s disease progressed but continued to benefit from subsequent use of anlotinib combined with toripalimab. DFS is 23 months to follow-up time. The results presented are the first to report the relationship between TMB and the efficacy of immunotherapy in STS. Based on our results, we hypothesis that anlotinib combined with toripalimab is effective for the treatment of some advanced ASPS or UPS. TMB may be a potential predictive biomarker for ICI treatment and deserves additional study.Soft-tissue sarcomas (STS), with over 100 different histologic subtypes, are rare tumors that account for 1% of all adult malignancies. Immune checkpoint inhibitors (ICIs) display certain benefits in some subtypes, especially in undifferentiated pleomorphic sarcoma (UPS), alveolar soft part sarcoma (ASPS), and leiomyosarcoma (LMS). However, efficacy is difficult to predict. High tumor mutational burden (TMB-H) and programmed death-ligand 1 (PD-L1) expression are the strongest features associated with the efficacy of immunotherapy, although they are rarely found in STS patients. Until now, whether or not PD-L1 expression and TMB are related to the efficacy of immunotherapy has not been determined. In this study, we report data obtained from two STS patients, one ASPS and one UPS with a high TMB, that benefited from anlotinib combined with toripalimab following resistance to anlotinib monotherapy. A 26 year-old female patient was diagnosed with ASPS. PD-L1 was negative. Next generation sequencing (NSG) revealed  Soft-tissue sarcomas (STS) are a rare and heterogeneous group of tumors that represent less than one percent of all adult malignancies . STS conIn this study, we report data obtained from one ASPS and one UPS patient with high TMB (TMB-H) following anlotinib resistance that received anlotinib combined with toripalimab therapy, and achieved a partial response (PR) and stable disease (SD), respectively. Our data suggest that TMB-H may be a potential predictive biomarker for immunotherapy.In July 2018, a 26 year-old female patient underwent bone emission computed tomography (ECT), positron emission tomography (PET), and magnetic resonance imaging (MRI) examinations for bone pain in our hospital. These examinations revealed a right thigh mass and abnormal activation of multiple focal bone metabolism, indicating a malignant bone tumor with metastases. In August 2018, a biopsy of tumor mass and a sacroiliac joint biopsy were performed. The pathological diagnosis report indicated that the mass on the outer right thigh was consistent with alveolar soft part sarcoma (ASPS) Figure 1In May 2018, a 63 year-old male patient came to our hospital due to cough and blood-streaked sputum. A CT scan revealed left lung nodules and lymphadenectasis in the mediastinum and left hilar and suspected metastasis of left adrenal nodule Figure 5ICIs, consisting of PD-L1, programmed cell death protein-1 (PD-1), and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibitors, have revolutionized the treatment of human solid tissue tumors . Some stTargeted therapy for sarcoma is largely achieved with small-molecule, multi-target, anti-vascular drugs, including pazopanib, regorafenib and anlotinib, approved for the treatment of different types of sarcomas –4. SinglASPS is an extremely rare subtype of STS, with only one diagnosis per 10 million people per year, accounting for approximately 0.5% of all sarcomas . AlthougImmunotherapy has shown preliminary influence in the treatment of sarcoma, however, clear predictive biomarkers remain uncertain. PD-L1 expression andTMB-H can predict the efficacy of immunotherapy in most tumors , 25, altA past study investigated the expression of PD-L1 in sarcoma and found a positive rate of only 12%; one positive outcome resulted from a radiation associated pleomorphic sarcoma and the other from a spindle cell sarcoma . AnotherTMB is often detected in various tumors and is related to the efficacy of ICI treatment . Yet, thAn Open-Label Phase IB trial found that the combination of toripalimab plus axitinib is tolerable and displays promising antitumor activity in patients with treatment-naive metastatic mucosal melanoma . The finTo our knowledge, this is the first report for the combination of anti-VEGF and PD-L1 inhibition for TMB-H STS. Our results are encouraging. However, the following limitations exist for our results : 1. We could not confirm whether or not the effect was due to a single immunotherapy or to the synergy of combined treatment. 2. Our case reports only provide preliminary conclusions, although they, at least, indicated that TMB-H may be a potential biomarker. 3. Specific reasons for effectiveness of the combined treatment remains elusive.Large randomized controlled trials should be conducted in order to examine the potential benefits of the PD-1/PD-L1 blockade, either alone or in combination with targeted therapy. To determine patients most likely to benefit from ICIs; and to evaluate TMB, the tumor microenvironment, gene expression, and genetic alterations, as well as to explore underlying cellular and molecular mechanisms, future studies are warranted.Anlotinib combined with toripalimab was shown to be an effective therapy in advanced STS or ASPS patients with metastases, specifically for TMB-H STS. Our study indicates that anti-VEGF TKIs combined with ICIs may be an effective choice for the treatment of STS or ASPS. The two cases examined suggest that TMB-H may be a potential predictor. This hypothesis will need to be tested in a larger clinical trial that encompasses robust correlative studies. The ongoing clinical trial NCT02609984, NCT02815995, and NCT02636725 will confirm the efficacy of ICIs and explore predictive marker.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics committee of Guangdong Provincial Hospital of Chinese Medicine. The patients/participants provided their written informed consent to participate in this study.Conception/Design: YL and HZ; Provision of study material or patients: YL and YHL; Collection and/or assembly of data: YQ, XC, and XQ; Data analysis and interpretation: YY, XD, and YC; Manuscript writing: YL and MX; Final approval of manuscript: YL and HZ. All authors have read and approved the submitted version of the manuscript.Authors MX and YC are employed by Shanghai OrigiMed Co., Ltd.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


CALD1 gene encodes CaD as multiple transcripts that mainly encode two protein isoforms: High-molecular-weight (h-CaD), expressed in smooth muscle, and low-molecular-weight (l-CaD), expressed in nonsmooth muscle cells. Most studies have suggested an oncogenic role of CaD in colorectal cancer, but the exact subcellular localization of the two CaD isoforms in tumor cells and stroma have not been clarified yet. Here, we analyzed tissue samples from 262 colorectal cancer patients by immunohistochemistry analysis using specific antibodies for l-CaD and h-CaD. The results showed elevated cytoplasmic expression levels of l-Cad in 187/262 (71.4%) cases. l-Cad was expressed at low levels in the normal colon mucosa and was also consistently expressed in the cancer-associated stroma of all cases, suggesting that it could play a role in modulating the tumor microenvironment. l-CaD expression in cancer cells was associated with preinvasive stages of cancer. Survival analysis indicated that patients with high l-CaD expression in tumor cells could respond poorly to selective chemotherapeutic 5FU, but not combination chemotherapy. h-CaD was expressed in colonic and vascular smooth muscle cells as expected and to a lesser extent in the tumor-associated stroma, but it was not expressed in the cancer cells or normal colon mucosal epithelial cells. Collectively, these data clarify how the expression patterns of CaD isoforms in colorectal cancer can have applications in the management of colorectal cancer patients.Colorectal cancer is a notorious disease, with almost half of the patients succumbing to the disease. The prevalence and incidence rates of colorectal cancer are increasing in many parts of the world, highlighting the need to discover new biomarkers for diagnosis and therapy. Caldesmon (CaD), an actin-binding protein that plays a significant role in controlling cell motility, has emerged as a promising biomarker. The  Almost half of the patients with colorectal cancer are destined to die of their disease , and thaCALD1 gene encodes CaD in multiple isoforms. High-molecular-weight CaD  is restricted to the smooth muscle cells of visceral and vascular origin, while the low-molecular-weight CaD  isoforms are expressed in nonsmooth muscle cells , retrieved from https://www.jamovi.org (accessed on 13 December 2022), and R Core Team (2021), R: A Language and environment for Statistical Computing (Version 4.0) [Computer software], retrieved from https://cran.r-project.org (R packages retrieved from the MRAN snapshot 1 April 2021).For the statistical analysis, we used the statistics interface Jamovi (v1.6, The Jamovi Project, Sydney, Australia, In conclusion, our data clarified which CaD isoform is expressed in colon cancer and its subcellular localization. Colorectal cancer cells overexpress l-Cad to various levels but not h-CaD. Moreover, l-CaD was consistently overexpressed in the tumor-associated stroma, suggesting that it plays a role in modulating the tumor microenvironment. l-CaD expression was high in the pre-metastatic stages, suggesting that it prepares the cells for invasion and metastasis, but its role becomes redundant after the cells have metastasized. I-CaD expression in colon cancer is associated with poor survival after 5FU therapy alone, but l-CaD did not show a significant effect on combination chemotherapy in this study. Thus, l-CaD could be a promising potential biomarker for the diagnosis and response to treatment in colorectal cancer.


This study investigated the relationship between serum lipid levels and clinical outcomes in acute myeloid leukemia (AML) by establishing a predictive risk classification model.A total of 214 AML patients who were pathologically diagnosed and treated with standard induction chemotherapy at Sun Yat-Sen University Cancer Center were included. The patients were randomly divided into the training (n = 107) and validation (n=107) cohorts. Univariate and multivariate Cox analyses were used to assess the value of triglyceride (TG), Apolipoprotein B (Apo B), Apo Apolipoprotein A-I (Apo A-I), cholesterol (CHO), and high-density lipoprotein (HDL) as prognostic factors for AML.P<0.05). The area under the curve of the novel model for five-year OS was 0.737. A nomogram was constructed to integrate the model with age and the 2017 ELN cytogenetic classification, with the merged model showing improved accuracy with an area under the curve of 0.987 for five-year OS.After a series of data analyses, a five-factor model was established to divide the patients into high- and low-risk groups. Kaplan-Meier survival analysis showed that the high-risk group had a poor prognosis (A novel model was constructed using a combination of the serum lipid profile and clinical characteristics of AML patients to enhance the predictive accuracy of clinical outcomes. The nomogram used the lipid profile which is routinely tested in clinical blood biochemistry and showed both specific prognostic and therapeutic potential. Acute myeloid leukemia (AML) is known for its complicated cytogenetics and pathological heterogeneity, its strikingly high relapse tendency, and is lethal in ~50% of young adults and ∼80% of older adults . Owing tLipids are important components of cell membranes and have been associated with the underlying mechanisms of cancer progression, including excess proliferation and aberrant signaling. In addition, lipid metabolism plays a key role in cellular energy supply and signaling, as well as other essential aspects of tumor cell proliferation. Due to the increased metabolism and proliferation of tumor cells, dyslipidemia is typically observed in various tumor patients with a variety of tumor types . A serieIn the present study, we investigated the role of lipid and apolipoprotein profiles as prognostic indicators in AML. Not only did we retrospectively analyze the lipid characteristics of AML patients and explore their value in predicting disease prognosis when combined with current clinical indicators, but we also developed a lipid profile-based model which was found to have improved prognostic precision.We performed a retrospective analysis of the clinical data of 273 AML patients. The inclusion criteria were patients who had been pathologically diagnosed with AML and were first treated in the Sun Yat-sen University Cancer Center (SYSUCC) between Dec 2000 and May 2021. The exclusion criteria were: a) patients with acute promyelocytic leukemia; b) patients who had previously taken or were regularly taking lipid-lowering medication, or who had a combination of chronic metabolic diseases such as diabetes mellitus, chronic renal failure, or abnormal liver function at the time of initial diagnosis; c) patients with missing lipid profile data; d) patients with incomplete follow-up data or whose survival periods were too short to analyze; e) patients with other malignant diseases. After the collection of information on treatment, a further 17 cases were excluded as they had not received the standard induction remission chemotherapy with cytarabine and DNR (Daunorubicin)/IDR(Idarubicin) . Finally, 214 patients were selected for analyses , apolipoprotein AI (Apo A-1), apolipoprotein B (Apo B), cholesterol (CHO), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), lactate dehydrogenase (LDH), body mass index (BMI), dates of diagnosis, death, or last follow-up, and cytogenetic risk classification based on the 2017 ELN criteria along with information on initial therapy. Laboratory examinations were performed on fresh blood samples obtained from patients after overnight (ON) fasting. The median duration between blood collection and treatment initiation was 14 days (3-25 days). This duration was not based on the patients’ OS.via hospital outpatient appointments or telephone conversations. Interviews were conducted once in six months for the first three years, and then annually to assess relapse or death. The last follow-up visit was dated July 31, 2021, to verify the final status of the study participants and to exclude those who could not be contacted. The primary endpoint was overall survival (OS), described as the duration of time between diagnosis and death for patients who had died or between diagnosis and the last follow-up for those that had survived.Following treatment, patients were monitored Threshold identification for prognostic indicators9/L), Apo-A1 (0.7 g/L), Apo B (0.65 g/L), CHO (2.67 mmol/L), TG (2.55 mmol/L), HDL (0.45 mmol/L), LDL (1.43 mmol/L), LDH (187.9 U/L), and BMI (19.3).To assess possible prognostic indicators among lipid and apolipoprotein profiles, X-tile software (3.6.1)16 was used to identify the optimal OS-based threshold. The patients were then stratified into low- (LR) and high-risk (HR) sub-cohorts. Univariate and multivariate Cox regression analyses were then used to identify potential independent prognostic values associated with the lipid profile. Optimum cutoff values were determined by X-tile as follows: Age (60 years), WBC  was used for all data analyses. Continuous variables were analyzed using one-way ANOVA and categorical variables by χhttp://www.R-project.org) was used for significance estimation.Subsequently, optimal weighting coefficients for the stand-alone prognostic indicators were identified using least absolute shrinkage and selection operator (LASSO) regression analysis. OS analyses were conducted using Kaplan-Meier (KM) curves. The prognostic power of the model was determined using time-dependent receiver operating characteristic (ROC) curves and areas under the curve (AUCs). These analyses were initially conducted in the TC followed by verification in the VC. A two-tailed P-value <0.05 was set as the significance threshold. R software  and VC (n=107) cohorts as described in the flow chart Figure 1p<0.05) while multivariate analysis showed that Apo A-I, Apo B, TG, CHO, and HDL were independent prognostic factors (p<0.05).The clinical characteristics were divided into categorical variables based on the optimum cut-off values, and univariate and multivariate analyses were performed to identify indices of prognostic value. Univariate analysis showed that the indices of the lipid profile, namely, Apo A-I, Apo B, CHO, TG, LDH, HDL, and LDL were significant prognostic factors (p<0.05)  in the entire group  in the TC. After calculation of the best weighting coefficients by the regularization parameter lambda and the 1-SE criteria  which are routinely measured in blood biochemical tests. After patients were stratified into HR and LR groups according to the lipid results, it was found that the HR group had poor prognoses. Due to the physiological characteristics of disease-sustaining leukemic stem cells, we further combined the RS with other factors including the broadly applied 2017 ELN cytogenetic classification to generate a nomogram. The time-dependent ROC curve illustrated that the merged model was more effective and that the merge significantly enhanced the predictive accuracy.Several studies have reported abnormalities in the plasma lipid profiles of leukemia patients , 9; howein vitro studies have suggested that certain genetic changes in leukemia cells are associated with enhanced dynamics and metabolism of lipid species in AML  level had a greater impact on the assigned score. Triglycerides play a pivotal role in the synthesis and utilization of fatty acids, which play important roles in the use of cellular energy, and an intermediate product of TG synthesis and utilization, diacylglycerol, acts as a second messenger in cellular signaling . It has Several studies have suggested that leukemia stem cells (LSCs) with the potential for self-renewal are responsible for disease sustainability, and traditional cyto-cycling or cytotoxic drugs are unable to target these relapse-related stem cells . It has On the other hand, since most of the chemotherapy drugs used for treating leukemia are highly toxic, their effects on liver and kidney functions cannot be ignored . The staAs described above, although the significance of lipid parameters in predicting survival has been confirmed, there were, nevertheless, some limitations to this process. When time-dependent ROC curves were applied in the entire patient cohort, we noticed that the AUCs of the three- and five-year RS values were below those of the 2017 ELN risk classification . ELN staging incorporates a variety of AML prognosis-related genes, including gene mutations related to lipid metabolism, and has been demonstrated to be a complete acute myeloid prognosis-stratified management system , 25. whiDespite the interesting data, this research has certain limitations. First, the data were collected over an extended period and it was not possible to evaluate them systematically using a unified assessment program. Second, all patient data were from a single institution, which may introduce potential bias. The sample population was relatively small and additional studies are warranted to assess whether the optimal threshold is applicable on a wider scale. Additional large, prospective, multicenter investigations would be needed to confirm our conclusions, and a quantifiable, clinically guided, and simply operationalized risk scoring system is currently lacking. Lastly, the possible molecular biological mechanisms involving lipid metabolism in AML development and progression and its therapeutic value remain to be systematically explored in a more specific manner.Using real-world clinical data as a foundation, a model was constructed using data on serum lipid profiles to estimate OS in AML patients. Lipid profiles can thus be used as new prognostic indicators to enhance the predictive precision of traditional factors including the revised 2017 ELN genetic risk stratification of AML and may promote the future study of incorporating lipid metabolism in the precision regulation of treatment regimens for patients with AML.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by Ethics Committees of Sun Yat-sen University Cancer Center. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.Study concept and design: HZW, SB, and RS; data collecting: JW and SL; statistical analysis: HZW, RS, and SB; figure and tables preparation: SB, HZW, and RS; writing-original draft: SB and HZW; data and tables inspection and validation: SB and BF; project administration: YL and HW; work supervision: YL and HW; Writing-review and editing: YL and HW; Funding acquisition; YL. Critical revision of the manuscript for important intellectual content: all authors. All authors contributed to the article and approved the submitted version.


Despite effective strategies to prevent substance use and substance use disorders among college students, challenges remain. As young adults’ preference for and comfortability with web-based technology continues to increase, leveraging innovative approaches to rapidly evolving mHealth technology is critical for the success of lowering the risk for substance use and related consequences in college populations, and especially those at Hispanic Serving Institutions. Therefore, the present study describes the rationale, development, and design of iSTART, a novel web-app to prevent substance use among students.The web-app was developed following the intervention mapping protocol, and in collaboration with numerous stakeholders, including a community-based partner specializing in substance abuse prevention and treatment. A 30-day multi-module web-app intervention was developed based on key theoretical constructs, behavior change strategies, and practical module components: attitudes (knowledge), perceived susceptibility (risk perceptions), subjective norms (normative re-education), and self-efficacy . This intervention will be evaluated via a time series design using a sample of 600 students randomly assigned to either the intervention, comparison, or control condition at a public institution in southern California.The iSTART web-app is an innovative and sustainable program ideal for college campuses with diverse student populations. If this prevention web-app is successful, it will significantly contribute to the evidence of effective substance use interventions in the college setting, and identify the benefits of mHealth programs to prevent future substance use.NCT05362357 retrospectively registered on May 4, 2022 on clinicaltrials.gov. Although the college years are a period of exploration and positive transformation, college students are at high risk for health-compromising behaviors such as alcohol and drug use. In 2020, approximately one-third of U.S. college students reported past-month binge drinking, 43% used marijuana, 16% used nicotine vaping devices, and 3% misused prescription drugs , 6. RelaResearch suggests the negative social, legal, and health-related outcomes linked to substance use may disproportionately affect some populations more than others. While non-Hispanic White young adults report the highest rate of overall alcohol consumption, Hispanic adults are more likely to have higher rates of alcohol dependence, and consume five or more drinks in one sitting than their non-Hispanic White peers , 12. MorIn response to the growing concern of young adult and college student substance use, the National Institute of Alcohol Abuse and Alcoholism (NIAAA) promotes and facilitates the adoption of evidence-based research focusing on individual-level alcohol intervention strategies implemented on college campuses , and theCurrently, only three of the nearly two dozen evidence-based individual-level alcohol and substance use intervention strategies listed by NIAAA are identified as highly effective and low cost: normative re-education, skills training, and personalized feedback  . AdditioDespite significant progress leading to the identification of modifiable risk and protective factors and effective strategies to prevent substance use and substance use disorders, challenges remain. Evidence-based practices are not being broadly adapted and sustained, and emerging drug trends  present new challenges for prevention research and practice –30. One There is a strong link between Healthy People (HP) 2030’s focus on reducing substance use among young people and the need to develop, test, scale, and sustain evidence-based programs. Especially programs designed to limit engagement in health-compromising behaviors, such as substance use; and prevent progression to risky use in service or educational systems. Importantly, HP 2030 identified the following primary public health objectives: reduce a) the number of adults who use marijuana daily or almost daily, b) the proportion of adults who use drugs in the last month, c) the number of people who misuse prescription drugs and, d) the number of young adults who binge drink; goals this study aims to address . This paThe design consists of participant recruitment and randomization of participants to either intervention, comparison, or control conditions with a time series evaluation design. The intervention will occur at a large Hispanic Serving public Institution in southern California. The students in the intervention group will receive a 30-day web-app consisting of five substance-specific modules, while the students in the comparison group will receive a single abbreviated module, and those in the control group will only have access to standard online University substance abuse resources. Study data collection periods consist of a baseline survey after recruitment and assignment to condition, an exit survey after completing the 30-day iSTART web-app intervention (or 30-day comparison or control), and a 90-day follow-up survey.The study population will consist of college students age 18–30. We will recruit 200 students in the prevention condition, 200 students in the comparison group condition, and 200 students in the matched control condition. We will use mixed models with a random effect for individual to test for the difference in longitudinal slopes with days drinking and marijuana use (example outcomes). We assume an average of 3 measurements per person and a correlation of 0.10 among intra-individual measurements, using a 2-sided test with alpha = 0.05 and 80% power, we will be able to detect a difference in frequency of alcohol and marijuana use at the final endpoint for prevention vs. control and for prevention vs. comparison group with Cohen’s d effect sizes of approximately 0.20 and 0.23, respectively, meaning we will be able to detect small minimum effect sizes among groups. Power analysis indicate that to detect a small effect size, adjusted for covariates across groups , a minimum of 525 participants are needed over three years. An oversampling of 15% will be conducted to account for possible attrition across surveys. A total sample of 690 college students  will be recruited over three years to achieve sufficient statistical power.Recruitment of student participants will include printed flyers with study information available on campus during tabling events for students at the beginning of the academic term, during campus events  with different campus organizations; posters on lawn signs, campus buildings, and businesses; and electronic posting on digital campus billboards. Students will be invited to participate via email recruitment fliers to Student Housing and through college and department announcements. All recruitment materials will include the intervention website information, where students can review the study requirements, check their eligibility, and enroll in the study. Initial screening of participants includes an electronic review of study objectives, completion of a brief questionnaire for alcohol use disorder (AUD) or substance use disorder (SUD) risk , and electronic consent. Exclusion criteria include: individuals who are not college students, under 18 or over 30 years of age, or at high risk for AUD or SUD. Students screened as high risk for AUD or SUD will be referred to additional resources and excluded from the study.The study adheres to the Belmont Report Ethical Principles and Guidelines for the Protection of Human Subjects of Research. Approval for the intervention study was provided by the Institutional Review Board.The intervention web-application consists of five weekly substance-specific modules that provide prevention information geared toward college students. The brief 15-minute web-app modules emphasize simplicity, interactivity, and accessibility. The development of each module’s prevention-related content is guided by evidence-based strategies. The intervention mapping protocol and its collaborative principles were used to develop the web-app , in addiDrugabuse.com), National Institutes of Drug Abuse (NIDA), drugabuse.gov, U.S. Food and Drug Administration (FDA), truth initiative, and Generation Rx. A licensed psychologist created short self-assessments for each substance module and developed corresponding feedback. Other stakeholders  were frequently consulted to provide insight on recommendations for healthy coping strategies/healthy alternative activities, suggestions for improving social wellbeing, and related campus resources accessible to students.Diverse stakeholders were engaged following the examination of needs assessment data and the intervention mapping protocol. To develop the content of the intervention, a partnership was formed with a local community-based organization (CBO) specializing in substance abuse prevention and treatment services. Alcohol, tobacco, and other drugs (ATOD) prevention specialists at the CBO created preliminary prevention messages for each substance-specific module including substance-related facts, health risk information, and safe use guidelines from numerous reliable substance abuse sources such as: NIAAA, Centers for Disease Control and Prevention (CDC), American Addiction Centers . They ensured all university accessibility requirements were met, and content was appropriately designed for diverse smart device viewing, usable from either a mobile phone, tablet, or laptop/computer. The application is hosted on a university server and leverages the already existing institutional identification management system, which ensures that participants use their university username and log-in, providing security and confidentiality.Health behavior theory constructs such as self-efficacy  and percThe 30-day prevention web-app consists of five weekly substance-specific modules: alcohol, marijuana, nicotine, prescription drugs, and illicit drugs. Each module contains a similar pattern of elements to address the aforementioned health behavior constructs, utilizing evidence-based behavior change strategies and interactive practical applications . Setting SMART goals  is a significant strategy frequently used in health behavior program planning and intervention development to provide participants criteria on how to create a behavior-specific goal with a well-defined measure for success , 56. EacThe 30-day iSTART web-app intervention is evaluated through a time series design. The study includes an eligibility screener, a baseline survey, a 30-day exit survey, and a 90-day follow-up survey . Students can log on using the web-app link embedded in the weekly module reminder email, or directly from the study website. Those in the intervention group have seven days to complete each substance-specific module, and upon completion receive the next module six days later. Those in the comparison group have 30 days to complete the single abbreviated substance module. All participants may contact study staff via email with questions or concerns, and have access to additional study information or support resources  on the study website. To address any technical errors or server support, study staff communicate with university IT staff directly.Amazon.com gift cards via email when they complete pre- and post-test surveys and web-app modules. Exit surveys are auto-administered via email from the web-app. The follow-up survey is emailed by study staff to participants 90 days after exit surveys are completed. Participants have two weeks to complete exit and 90-day follow-up surveys. Those in the intervention group receive a total of $100: $15 for baseline, $15 for modules 1 and 2, $15 for modules 3 and 4, $25 for module 5 and the exit survey, and $30 for the 90-day follow-up survey. Comparison group participants receive a total of $75: $15 for baseline, $15 for the single module, $15 for the exit survey, and $30 for the 90-day follow-up survey. The control group receives a total of $65: $15 for baseline, $20 for the exit survey, and $30 for the 90-day follow-up survey.Incentives are provided to ensure participation and retention. Participants receive Substance use behavior will be assessed at baseline, exit, and 90-day follow-up as required by SAMHSA’s Center for Substance Abuse Prevention (CSAP) Government Performance and Results Act (GPRA) adult questionnaire . This inery likely to 4 = very unlikely. A measure of substance use intention is necessary to determine the effectiveness of the web-app intervention on preventing or reducing participants’ intent to use; and is commonly used in behavior change theory research to determine actual use . This will determine whether the slopes of substance use are less steep among prevention participants than comparison and control group students.All data is collected online using Qualtrics, a fully HIPAA compliant software licensed by the university . To asseknowledge, will predict flat or slower increases in substance use, by including knowledge as a time-varying variable in the within-person model. Including individuals’ mean knowledge in the between-person intercept equation, and by group-mean centering the knowledge within the time-level equations, analyses separate out between-person differences, allowing for an assessment of within-student change in knowledge and its relation to substance use within the study period. This analytic approach can account for stable, between-student differences and potential bias associated with unmeasured, between-person factors that influence outcome behaviors [Generalized linear models will also test hypotheses that growth in mediators, for example increases in ehaviors , 81.Despite effective strategies to prevent substance use and its disorders, evidence-based practices are not being broadly adapted and sustained. Coupled with emerging trends in opioids and vaping –30, the During the development of the iSTART web-app, multiple strategies of intervention mapping were utilized, and numerous stakeholders were conferred. By including evidence-based theoretical constructs, and individual-level behavior change strategies that are practically applied and targeted toward substance use prevention among college students, we believe the iSTART web-app is an innovative and sustainable program ideal for college campuses with diverse student populations. If this prevention web-app is successful, it will significantly contribute to the evidence of effective substance use interventions in the college setting, and identify the benefits of web-app programs to prevent future substance use.


Compared to the 3-month assessment, individuals with c-SCI displayed structural, functional, and mechanical changes during the 6-month assessment, including significant reductions in end diastolic volume , stroke volume , myocardial contractile velocity (S') , and peak diastolic longitudinal strain rate , and increased early diastolic filling over early myocardial relaxation velocity (E/E') ratio . These indices did not significantly change in individuals with tl-SCI between time points. Ejection fraction was different between individuals with c-SCI and tl-SCI at 3  and 6 months , though values were considered normal. These results demonstrate that individuals with c-SCI exhibit significant reductions in cardiac function from 3 to 6 months post-injury, whereas individuals with tl-SCI do not, suggesting the need for early rehabilitation to minimize cardiac consequences in this specific population.Individuals with cervical spinal cord injury (SCI) experience deleterious changes in cardiac structure and function. However, knowledge on when cardiac alterations occur and whether this is dependent upon neurological level of injury remains to be determined. Transthoracic echocardiography was used to assess left ventricular structure, function, and mechanics in 10 male individuals  with cervical ( Left ventricular (LV) atrophy and decreased volumes are well documented in individuals with chronic spinal cord injury (SCI) . DecreasSimilar to SCI, microgravity exposure during spaceflight has been associated with an overall physiological decline, providing a potential model to better understand the alterations in these specific populations over time . While tNo study to date has examined the longitudinal changes in cardiac function post-SCI in the sub-acute setting , stratifying for neurological level of injury (NLI). Thus, the aim of this present longitudinal case series was to investigate changes in LV structure, function, and mechanics, in individuals with cervical SCI and thoracolumbar SCI at 3- and 6-months post-injury using transthoracic echocardiography (TTE) .Clinical protocols were approved by the University of British Columbia Clinical Research Ethics Board (H13-03072) and conducted in accordance with the second Helsinki Declaration. The participants provided written informed consent prior to data collection. The NLI and the severity of SCI were classified according to the International Standards for Neurological Classification of SCI (ISNCSCI) by a trained physician  . ParticiTTE was performed on a commercially available ultrasound  and stored for offline analysis using specialized computer software  according to the recommendations of the American Society for Echocardiography (ASE) , by a siThe average of three cardiac cycles was used to determine LV structure and functional indices. Measures of LV structure at end-diastole and end-systole were reported from the parasternal long-axis views, and used to derive relative wall thickness . VolumetIndices of LV mechanics were derived from apical four-chamber and parasternal short-axis images at the level of the mitral valve , papillary muscle (mid), and apex . Images were analyzed using 2D speckle-tracking software in accordance with recommended guidelines . Raw speP ≤ 0.05. Wilcoxon signed rank test were used to analyze outcomes between time points within groups. Group differences were analyzed using the Mann Whitney U-test. Results are presented as median with upper and lower quartiles . Graphical representations were made in Prism , SPSS, and Adobe Illustrator .Data are presented as raw values and percentages. Statistical analyses were performed using Statistical Package for Social Science software  with statistical significance set at n = 5) or thoracolumbar SCI (n = 5) were included. TTE was conducted 79 days (65–108) and 204 (191–218) post-injury. Demographics are highlighted in A total of 10 male participants  with motor-complete (AIS A/B) cervical SCI  , end-systolic volume (ESV) , SV , S' , and increased E/E' ratio  for individuals with cervical SCI. For LV diastolic mechanics, longitudinal strain rate was lower in the cervical group at three compared to 6 months    . These iP < 0.01), which was still within the normal range of 52–72% for males as per ASE guidelines . While a recent meta-analysis demonstrated that structural and functional changes are apparent for individuals with chronic SCI compared to non-injured individuals , these cReductions in LV structural and functional cardiac indices were found for individuals with cervical SCI between 3- and 6-months post-injury, whereas these changes were not apparent for individuals with thoracolumbar SCI. As the LTPA measures were highly variable but somewhat comparable amongst the cervical SCI and thoracolumbar SCI participants, the most likely explanation for the differences between groups can be attributed to the disrupted supraspinal regulation of sympathetic activity to the heart following cervical SCI . To suppDespite reductions in LV structure and global function in the cervical SCI group, indices of LV systolic mechanics were similar over time. Perhaps this can be attributed to a mechanical compensation post-SCI to maintain systolic function in the cervical SCI group. The observation of preserved systolic mechanics and reduced SV has been previously reported , and is . Therefore, self-reported minutes of moderate-to-vigorous-intensity physical activity do not reflect actual time spent performing activities at higher intensities as measured objectively via a heart rate monitor. Therefore, In-keeping with other results, it could be implied that individuals with SCI do not reach an effective cardiovascular training threshold to improve neurologic, cardiovascular, or musculoskeletal health during inpatient therapy . The patients/participants provided their written informed consent to participate in this study.MW and AK had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. SB, TN, MW, KC, and AK contributed to conception and experimental design. SB acquired the data. SB, TN, and MW analyzed the data. SB, TN, KC, CW, TT, MW, and AK interpreted the data. SB and TN drafted the manuscript. SB, MW, TN, KC, CW, TT, and AK contributed to editing the final version of the manuscript. AK is the principle investigator of the project. TN and MW co-supervised the project. All authors contributed to the article and approved the submitted version.This work was supported by a grant  from the Craig H. Neilsen Foundation (Grant H13-03072), the Canadian Foundation of Innovation , and the BC Knowledge Development Fund . SB was supported by The Robert H.N. Ho Scholarship, UBC President's Academic Excellence Award, and Peter McLardie Award (Sonography Canada). TN was supported by a Postdoctoral Research Trainee Award from the Michael Smith Foundation for Health Research (MSFHR) in partnership with the International Collaboration on Repair Discoveries, (Grant Number: 17767). KC was supported by a Craig H. Neilsen Foundation Postdoctoral Fellowship (Grant Number: 281863). MW was supported by a Postdoctoral Research Trainee Award from MSFHR in partnership with the Rick Hansen Foundation (Grant Number: 17110). AK holds the Endowed Chair in Rehabilitation Medicine.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Isothermal amplification (IA) is a nucleic acid amplification technology (NAAT) that has contributed significantly to the healthcare system. The combination of NAAT with a suitable detection platform resulted in higher sensitivity, specificity, and rapid disease diagnosis. Traditional NAAT, such as polymerase chain reaction (PCR), is widely applied in the general healthcare system but is rarely accessed in resource-limited hospitals. Some IA methods provide a rapid, sensitive, specific, and simple method for disease diagnosis. However, not all IA techniques have been regularly used in clinical applications because different biomarkers and sample types affect either the enzyme in the IA system or sample preparation. This review focuses on the application of some IA techniques that have been applied in the medical field and have the potential for use at points of care.  Isothermal amplification (IA) is a technique for amplifying nucleotide chains using a simple temperature controller, and it is potentially used for point-of-care testing in fields or general laboratories. The major difference between IA and polymerase chain amplification (PCR) is that IA is performed at a constant temperature, whereas PCR requires a temperature-changing system. Another important difference between IA and PCR is that polymerase enzymes normally extend primers on a single strand of the dsDNA template during PCR. In contrast, some IA systems have a special polymerase enzyme that can directly extend primers on a double strand of dsDNA during the amplification process. In addition, some IA techniques, such as rolling circle amplification (RCA), have the ability to use DNA/RNA targets as primers and designed ssDNA/RNA as a template, as shown in There are three key components of the IA system: (1) nucleic acid templates, (2) the initial primer for complementary binding to the target nucleic acids, and (3) isothermal enzymes for nucleic acid amplification. Both PCR and IA require DNA templates, primers, nucleotide substrates, and amplification enzymes. PCR templates are mostly dsDNA, which require a thermal cycle step to denature, anneal, and elongate the template and amplify the final dsDNA products. The templates for the IA system can be ssDNA, dsDNA, and RNA. Moreover, in the padlock probe-based RCA, one of the IA systems, the short target RNA can subsequently be used as a primer for RCA reaction, thereby linearly amplifying the target sequence in a process that has been shown to be highly quantitative. Some IA systems, such as recombinase polymerase amplification (RPA) and strand displacement amplification (SDA), can use dsDNA as a template and require single stranded binding protein (SSB), recombinase enzyme, and isothermal polymerase enzyme for strand separation and elongation. The significant advantages of the IA system are the ability to amplify nucleic acids using a simple thermal controller system and the simple operation requiring only less skilled staff to perform the test. Therefore, the IA system can be potentially applied for onsite testing in remote hospitals and healthcare settings. This review focuses on the applications of current IA techniques, such as LAMP, RCA, and CRISPR-Cas systems in the medical field. Bst DNA polymerase, and a set of four to six specific primers that recognize six to eight different regions of the target DNA. LAMP was first described in 2000 by Notomi et al. as a nucleic acid amplification technique with simplicity, high specificity, efficiency, and speed at a constant temperature  In princThe LAMP mechanism is illustrated in Leptospira DNA . Brimination ,11.RCA was first described in 1995  as an isIn nature, the RCA reaction is a process of genomic replication, which can rapidly produce multiple copies of circular nucleic acid molecules, such as bacteriophage genomics and plasmids of viruses ,13. TherRCA products can be monitored and read using various technologies. Among these, gel electrophoresis is the conventional procedure for RCA product analysis . HoweverMycobacterium tuberculosis by Schopf et al. DNA capture probes were immobilized on Sepharose beads. Subsequently, dsDNA was denatured and separated into two single strands before hybridization with capture and padlock probes. Ligation and circularization steps were then initiated, and the target DNA was amplified by RCA reaction using phi29 DNA polymerase. Following the reaction, the target DNA was labeled with two fluorescently labeled (FAM and Cy3) oligonucleotide probes for imaging. M. tuberculosis genomic DNA was detected using this method. Next, long- and double-stranded DNA were digested with restriction enzymes into small fragments. The DNA fragment was then denatured, and the RCA reaction was performed in the same manner as for dsDNA detection. The limit of detection of this platform was 4.25 fM of target dsDNA and 10,000 cfu/mL of M. tuberculosis . Th. Th37]. CRISPR-Cas systems are groups of DNA sequences found in the genomes of prokaryotic organisms that serve as adaptive immunity against bacteriophages, viruses, and foreign genetic materials, such as plasmids . CurrentCRISPR-associated protein (Cas) 9 is an RNA-programmable DNA-targeting and editing tool that serves as an adaptive immune system in bacteria and archaea. The CRISPR-Cas9 system consists of two major components: Cas9 enzyme, an RNA-guided DNA endonuclease enzyme, and guide RNA (gRNA), a short nucleotide (20 nucleotides) that has a complementary sequence to the target double-stranded DNA (ssDNA) . CRISPR-CRISPR-Cas9 has been used as a detection method for miRNAs with low cost, high specificity, and sensitivity . The novCRISPR-associated protein (Cas) 13 is an RNA-guided RNase composed of four members: Cas13a, Cas13b, Cas13c, and Cas13d . The strSpecific high-sensitivity enzymatic reporter unlocking (SHERLOCK), a CRISPR-based platform for the ultrasensitive detection of DNA or RNA, was first established in 2017 by Zhang et al. SHERLOCK is the technique that combines the nucleic acid pre-amplification method, which is an isothermal-based amplification, and CRISPR-associated protein 13 (Cas13)-based detection, which can bind and cut the sequences through endonucleolytic activity . 3 copies/mL. In addition, SHERLOCK was able to detect single nucleotide polymorphisms (SNPs) and mutations in cell-free DNA (cfDNA). However, this technique has some limitations. The system is not user-friendly, requires a fluorescence detector for signal readout, and the results are not quantitative.The second version of SHERLOCK has been developed to overcome these limitations and is called SHERLOCK version 2 or SHERLOCKv2. The new version of SHERLOCK was further developed under four conditions: a multiplexed detection platform for four targets, quantitative analysis, increasing signal sensitivity, and integration with the lateral flow for easy readout . After tCRISPR-associated protein (Cas) 12, an RNA-guided DNase enzyme, functions as a prokaryotic defense mechanism and comprises diverse family members . The strDETECTR, is a sensitive DNA detection platform using CRISPR-Cas12a, developed in 2018 by Doudna et al. DETECTR is a one-pot DNA detection method that couples isothermal amplification, enhancing the sensitivity, and Cas12-based detection [DNA endonuclease-targeted CRISPR trans-reporter, or etection . In prinetection . Furtheretection .During the pandemic of SARS-CoV-2, or COVID-19, the DETECTR technique, coupled with lateral flow technology, was developed as a rapid detection platform for SARS-CoV-2 viral nucleic acids . RNA wasAll-In-One Dual CRISPR-Cas12a or AIOD-CRISPR, a novel CRISPR-Cas-based detection platform with rapid, high sensitivity, and specificity for nucleic acids was developed by Liu et al. . In thisTo lower the LOD, many published CRISPR biosensing methods require nucleic acid amplification prior to CRISPR sensing. Among biosensing strategies, CRISPR-Cas systems exhibit high sensitivity and specificity and are simple and rapid. The trans-cleavage activity of Cas12 effector proteins is considered a novel potential biosensing application because of its shorter reaction time, high sensitivity, specificity, programmability, and universal applicability. To achieve an ultrasensitive CRISPR sensing platform, combining nucleic acid amplification strategies is often necessary, particularly isothermal amplification.Pseudomonas aeruginosa. The principle of CIA is based on LFB detection of a biotinylated ssDNA reporter. Samples were amplified by LAMP to improve assay sensitivity. The CRISPR-Cas12 reaction was subsequently demonstrated to enhance the trans-cleavage of Cas12 to cleave the specific target and ssDNA reporter. Reporter cleavage was captured by gold nanoparticle-streptavidin (AuNP-SA) to form the AuNP-SA-biotin ssDNA reporter complex. The complex was captured by a DNA probe, which is a DNA sequence complementary to the reporter, and immobilized at the test line. The excess complex subsequently interacted with biotinylated rabbit polyclonal anti-IgG antibody in the control line. The concept of this approach is that in the presence of target DNA, a trans-cleaved ssDNA reporter cannot bind to a complementary DNA probe immobilized on the LFB test line, resulting in the absence of the test line.CRISPR/Cas combining loop-mediated isothermal amplification, namely CIA, was developed in 2020 by Mukama and his colleagues . They inP. aeruginosa acyltransferase gene, 1 cfu/mL plasmid containing E. coli DH5α pure cultures. This assay did not show cross-reactivity with other nontarget bacteria. The result can be read by the naked eye after 15 min of LAMP amplification, 30 min of Cas12 reaction, and 5 min of LFB readout.The presence of a test line indicates the absence of a target. The performance of CIA-based LFB exhibits ultrasensitive detection by detecting as low as a single copy-cloned Listeria monocytogenes with the LOD as low as 0.68 aM (genomic DNA) and 26 cfu/mL (pure cultures). The concept of RAA-based E-CRISPR is illustrated in An alternative method, the CRISPR/Cas 12a based electrochemical platform (E-CRISPR), was developed by Dai and co-workers in 2009 for the detection of bacterial DNA . They inThe combination of CRISPR-Cas12a with rolling circle amplification (RCA) has been demonstrated for the detection of miRNAs by Min Qing et al., who also integrated this system with an immobilization-free electrochemical biosensing platform . First, IA is a powerful polymerization technique with high specificity and sensitivity for disease diagnosis. IA is an efficient target nucleic acid amplification strategy, which is resilient and flexible in diverse approaches. The rational pre-design of probe sequences  can provide multiple functions. IA can be used to detect genomes, proteins, and single cells. In the biomedical field, compared with conventional methods, IA is less time-consuming and less complex in terms of operation. Therefore, IA can be a highly efficient approach for rapid point-of-care diagnostic techniques. All the current applications of the isothermal amplification technologies and the relevant references are shown in Importance: Although PCR is widely used in the general healthcare system, it is rarely used in resource-limited hospitals because of the requirement of skilled staff and thermocycle controller systems. Therefore, IA, which is a technology that amplifies nucleic acids using a simple thermal controller system and requires only less skilled staff to perform the test, is potentially applied for onsite testing in remote hospital/healthcare. Current understanding and challenges: Three popular IA techniques, the LAMP, RCA, and CRISPR systems, have been continuously developed for disease diagnosis. Among these three IA systems, LAMP has been widely used for POC applications because of the short amplification times. However, there are two big challenges waiting for improvement, which are non-specific amplification and primer-dimer formation. For the RCA, it is notable for highly sensitive and selective detection. In particular, the ability to perform the reaction at a low temperature without the requirement of an initial denaturation. However, optimally designed circular DNA or RNA templates are required. Considering the CRISPR-Cas systems, they are high sensitivity and specificity diagnosis platforms, but their operation times are defective. As one IA technique is not suitable for all target molecules and sample types, optimization and clinical evaluation are required to achieve QC/FDA authorization. Future direction: Different biomarkers and sample types are somewhat affected, either by enzymes in the IA system or sample preparation, leading to only a few IA techniques being used for disease detection. Therefore, optimization of sample preparation and enzyme engineering to obtain specific binding and special activity in each individual IA system is required. To push new IA technologies into the market, strategic communication on this topic with the QC/FDA regulation sector is also necessary.


Paclitaxel (PTX) is a broad-spectrum chemotherapy drug employed in the treatment of a variety of tumors. However, the clinical applications of PTX are limited by its poor water solubility. Adjuvants are widely used to overcome this issue. However, these adjuvants often have side effects and poor biodistribution. The smart drug delivery system is a promising strategy for the improvement of solubility, permeability, and stability of drugs, and can promote sustained controlled release, increasing therapeutic efficacy and reducing side effects. Polymeric prodrugs show great advantages for drug delivery due to their high drug loading and stability. There has been some groundbreaking work in the development of PTX-based stimulus-sensitive polymeric prodrug micelles, which is summarized in this study. We consider these in terms of the four main types of stimulus ). The design, synthesis, and biomedical applications of stimulus-responsive polymeric prodrugs of PTX are reviewed, and the current research results and future directions of the field are summarized. Paclitaxel (PTX) was first discovered in the late 1960s. It is a natural substance derived from the needles and bark of the Pacific yew tree. It is a mitotic inhibitor used primarily in cancer chemotherapy, which can be used in the treatment of various cancers, including ovarian cancer, esophagus cancer, small and non–small-cell lung cancer, multiple myeloma cancer, bladder cancer, breast cancer, head and neck cancer, colon cancer, and Kaposi’s sarcoma . PTX is In recent years, the use of self-assembling nanoparticles of amphiphilic polymers has become common in drug delivery as they are able to act as carriers for the hydrophobic molecules of insoluble drugs . Compare2O2 is 0.001–0.7 μM in healthy cells, while it is 10–100 μM in tumor cells  and endogenous signals  have been extensively exploited in the design of polymeric prodrug delivery systems for triggered drug release . The pH or cells . ROS-senAs far as we know, much of the pioneering work on stimulus-sensitive polymeric PTX prodrug nanomedicine has not been well summarized. As shown in Compared with that of normal tissue, the tumor microenvironment is highly acidic, which is due to the high metabolic activity of tumor cells. Therefore, the development of pH-sensitive polymer-PTX prodrugs in which drug release is triggered by the acidity of tumor cells has attracted extensive attention. To achieve this, acid-sensitive organoleptic groups, such as acetals and acyclic ketals, are typically built into polymeric prodrug delivery systems to cause the release of the drug when the delivery system encounters an acidic microenvironment. For instance, Zhai et al. developed pH-sensitive polymer-PTX prodrug micelles by grafting PTX onto the main chain of poly (ethylene glycol) (PEG)-polycarbonate through an acetal-linker to accelerate drug release in tumor cells. The drug loading of PTX reached up to 33% . mPEG-PCThis self-assembled prodrug has excellent stability with drug loading up to 60.3% . Acyclicin vivo. This disulfide-bridged prodrug exhibited selective cytotoxicity toward tumor cells and enhanced tumor suppression in BALB/C mice bearing 4T1 tumor. Xie et al. reported a reduction-sensitive prodrug of PTX (PTX-S-BDP) by linking PTX and BODIPY (BDP-OH) using a reduction-sensitive linker for fluorescence imaging–guided chemotherapy  containing enzyme-sensitive GFLG oligopeptide (T1 contrast agent of Gadolinium-tetraazacyclododecanetetraacetic (Gd-DOTA) and the NIR fluorescent molecule pheophorbide a (Ppa) were conjugated to the polymer for cancer diagnosis, treatment, and real-time monitoring. In addition, an amphiphilic block copolymer prodrug, poly [oligo (ethylene glycol) methyl ether methacry-late] (polyOEGMA)-functionalized PTX, containing cathepsin B–sensitive GFLG oligopeptide linker between the PTX and the polymer backbone was constructed benzyl by introducing the benzylboronic ester linker between the PTX and the PEG (PEG-B-PTX)  . The loaG-B-PTX) . Lu et aG-B-PTX) . Then, tG-B-PTX) . PLP-NPsG-B-PTX) . To incrG-B-PTX) . The thrG-B-PTX)  (Wang K.G-B-PTX) , and comG-B-PTX) . Under lThe presence of the polymer shell stabilizes the polymer-based drug delivery system. Thus, they have the advantages of controlled PTX release, reduced dosage, and reduced systemic side effects. However, polymer-based drug delivery systems have some limitations. Organic solvents or surfactants, such as those often used in the preparation of polymer nanoparticles, can disrupt biological membranes and have significant interaction with certain proteins. At the cellular level, polymer-based nanodrug delivery systems are not as biocompatible as liposomes. The structure of polymeric nanoparticles is unstable, and the encapsulation of a large amount of PTX can lead to colloidal transformation. There is a main disadvantage that polymer nanoparticles lack selectivity toward tumor cells. Although nanoparticles can passively target solid tumors through the EPR effect, the majority of polymer prodrugs nanoparticles with the size range from 100 to 500 nm will still be cleared by the reticuloendothelial system. Active targeting can achieve specific uptake of tumor cells, further improve drug utilization, and reduce side effects. Polymers are generally modified targeting functional groups by chemical reaction to achieve active targeting.From the reviewed studies, it can be seen that a number of biocompatible polymers have been used and characterized for PTX prodrug formulation . AmphiphThe application of nanotechnology to cancer treatment has led to several breakthroughs previously and continues to flourish as a key component of the health care system. Abraxane is the only nano-PTX formulation approved by the FDA and EMEA for the treatment of cancer, and is the most successful PTX formulation in clinical research. In this review, we have focused on amphiphilic polymer-PTX prodrug delivery systems and their ability to provide stimulus-sensitive therapeutic nanoplatforms for intracellular on-demand drug release. Polymeric prodrug nanoparticles can not only greatly improve the drug loading and solubility of PTX but can reduce its toxicity. In the future development of more promising nano-prodrug PTX formulations, some challenges will need to be overcome. Among them, there is the need to improve the efficiency of drug enrichment and the specificity of its release at the lesion site.Despite this, the efficacy remains low for the prodrugs developed thus far. This may be due to the multilevel and complex biological issues inherent in attempting to eliminate cancerous tissues with minimum harm to the human body. Achieving this end requires targeted nanocarriers with strong specificity. To sum up, the research discussed in this review has made advances but there are still limitations to overcome. We hope that this overview will provide some ideas for future nano-prodrug delivery systems.