Background: Human albumin, a vital plasma protein with diverse molecular properties, has garnered interest for its therapeutic potential in various diseases, including critical illnesses. However, the efficacy of albumin infusion in critical care and its associated complications remains controversial. To address this, a review of recent meta-analyses was conducted to summarize the evidence pertaining to albumin use in critical illness. Methods: Adhering to the rapid review approach, designed to provide a concise synthesis of existing evidence within a short timeframe, relevant meta-analyses published in the last five years were identified and analyzed. PubMed, Embase, and Cochrane databases of systematic reviews were searched using pre-defined search terms. Eligible studies included meta-analyses examining the association between albumin infusion and outcomes in critically ill and perioperative patients. Results: Twelve meta-analyses were included in the review, covering diverse critical illnesses and perioperative scenarios such as sepsis, cardiothoracic surgery, and acute brain injury. The analyses revealed varying levels of evidence for the effects of albumin use on different outcomes, ranging from no significant associations to suggestive and convincing. Conclusions: Albumin infusion stabilizes hemodynamic resuscitation endpoints, improves diuretic resistance, and has the potential to prevent hypotensive episodes during mechanical ventilation in hypoalbuminemic patients and improve the survival of patients with septic shock. However, caution is warranted due to the methodological limitations of the included studies. Further high-quality research is needed to validate these findings and inform clinical decision-making regarding albumin use in critical care. Albumin is the most abundant plasma protein in humans and has long been recognized for its essential physiological functions in maintaining fluid balance, transporting molecules, and regulating pH. The therapeutic use of albumin is of significant interest because of its unique molecular characteristics, including its substantial antioxidant properties, versatile binding capabilities, and potential for targeted drug delivery . UnderstCritical illness is a consequence of inflammation that causes progressive organ dysfunction . It evenThe use of human albumin (HA) infusion has been extensively discussed for the management of critical illnesses and their associated complications . HA infuMeta-analyses play a crucial role in making informed clinical decisions as they combine all available data to provide the highest level of evidence . HoweverThis article is a compilation of existing studies and does not include any novel research involving human participants or animals. As a rapid review , it follPubMed, Embase, and Cochrane databases of scientific articles were searched for meta-analyses related to HA infusion from 1 January 2018 to 11 July 2023. The search was limited to studies published within the last five years, specifically from 2018 onwards. No language restrictions were applied. The identified articles were imported to Zotero, and duplicates were removed. In addition to the electronic search, manual identification of relevant meta-analyses was conducted using published reference lists. The search terms are listed in Meta-analyses of both RCTs and observational studies (cohort and case-control studies) investigating the association between HA use and mortality rates or other clinical and hemodynamic outcomes in critically ill perioperative patients were included. Articles containing multiple meta-analyses were eligible, and each meta-analysis was independently assessed for inclusion. The meta-analyses were identified based on the pre-defined eligibility criteria. Eligible studies should include all meta-analyses on HA infusion for the management of critically ill and perioperative patients. The exclusion criteria were as follows: (1) duplicated papers; (2) comments, guidelines, protocols, and editorials; (3) narrative reviews; (4) systematic reviews without meta-analyses; (5) network meta-analyses; (6) studies in which the target population was diagnosed with cirrhosis, not perioperative patients, or not critically ill; and (7) studies where HA treatment was not given. The publication of studies in the form of abstracts was not an exclusion criterion. There were no limitations on the publication language or date.The following information was extracted from the included meta-analyses and recorded in a pre-designed table: first author, publication year, country, type and number of included studies, type and number of patients in the treatment and control groups, type of interventions employed in the treatment and control groups, objectives or indications of HA treatment, study heterogeneity, and random effects with a 95% confidence interval (CI).Due to missing data, the authors of one of the studies  were conThe methodological quality of the included meta-analyses was assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool . This top-values, small-study effects, between-study heterogeneity, and concordance between the effect estimate of the largest study and the summary estimate of the meta-analysis. Heterogeneous data were used for descriptive purposes to highlight the variability and potential sources of inconsistency in the results.The evidence level of the association between HA use and patient outcomes was determined for each meta-analysis. The criteria were based on statistical significance by random- or fixed-effects p < 0.001; (2) no small study effects or large between-study heterogeneity; and (3) concordance between the effect estimate of the largest study and the summary effect of the random-effects meta-analyses.Convincing evidence: (1) statistical significance at p < 0.05; (2) 95% PI included the null hypothesis; and (3) no small study effects or large between-study heterogeneity.Suggestive evidence: (1) statistical significance of random effects at p < 0.05; (2) small study effects or large between-study heterogeneity were found.Weak evidence: (1) statistical significance of random effects at p > 0.05).Non-significant association: There was no statistical significance for the random effect of the meta-analysis , 10.5). Detailed information on patient numbers was missing for two meta-analyses that were published only as abstracts ,22. Ten Two meta-analyses, Lewis et al.  and MartThe review by Lewis et al.  includedMartin and Bassett  identifiA third meta-analysis by Itagaki et al.  investigTwo meta-analyses, Geng et al.  and Zou The results of Zou et al.  for patiGeng et al.  includedThree meta-analyses conducted by Keshavarz et al. , SiemensThe study by Keshavaz et al.  includedSiemens et al.  evaluateIn addition to the study by Itagaki et al.  on the mLee et al.  exploredChamarthi et al.  also focTwo studies analyzed the role of HA administration in two different neurological conditions: ischemic stroke and traumatic brain injury (TBI) ,25.In the case of ischemic stroke, a meta-analysis of four studies was conducted to evaluate the neurofunctional outcomes of patients treated with albumin therapy. The analysis revealed no statistically significant difference in the long-term neurological function between the albumin and control groups. Furthermore, there was concern about the occurrence of complications, such as pulmonary edema, after albumin infusion. Therefore, the administration of albumin therapy for acute ischemic stroke should be approached cautiously .Patients with TBI often experience hypoalbuminemia and require fluid resuscitation. The use of HA for TBI is controversial , and theHypoalbuminemia is frequently observed in hospitalized patients and is associated with several diseases . In hypoThe results of the assessments of the methodological quality of the meta-analyses are shown in For the nine non-critical questions, the following findings were observed: all the included meta-analyses specified their inclusion and exclusion criteria, including the population, interventions, comparators, and outcomes (Q1), and explained their study design for inclusion criteria (Q3); one meta-analysis did not perform study selection in duplicate  and the A meta-analysis by Lewis et al.  combinedA meta-analysis by Lee et al.  from TaiIn general, the methodological quality varied among the studies, with some being rated as high quality while others were considered critically low quality. Of the assessed meta-analyses, only two studies rated ‘high quality’ ,23:A metThe majority of the included meta-analyses were AMSTAR-2, rated as ‘critically low’ ,19,24,25Two studies exhibited intermediate quality and were rated ‘low’ ,20.Itagaki et al.  from JapIn the second ‘low-quality’ meta-analysis by Zou et al. , the usep < 0.001, absence of heterogeneity between included trials, no small study effect, and concordance between the effect estimate of the largest study and the summary effect of the random-effects meta-analyses) for an association of HA use with outcome versus crystalloids was found for CI as hemodynamic resuscitation endpoint in critically ill patients [p < 0.05, significant heterogeneity p < 0.05) for increases in MAP and CVP with HA administration [p < 0.05, no heterogeneity p > 0.05) for this outcome. The methodological quality of the study by Itagaki et al. [‘Convincing evidence’  in the SAFE-TBI study might have been suboptimal for patients with TBI. Experimental studies have directly compared commercially available hypotonic 4% HA used in SAFE with isotonic 4% HA  and revealed a higher ICP with hypotonic HA, suggesting that tonicity rather than albumin itself may impact ICP [The potential impact of HA on mortality in TBI remains uncertain, and the current evidence presents mixed findings. In the ‘Balanced Solution Versus Saline in Intensive Care Study’ (BaSICS), where hypotonic balanced crystalloids were compared with 0.9% saline, TBI patients treated with saline showed significantly better 90-day survival . In contpact ICP . Thus, tNo recent meta-analysis has specifically addressed hypoalbuminemia, KRT, or burns. Previous studies provided important evidence regarding these topics. These findings suggest that hypoalbuminemia is associated with worse outcomes, and the administration of HA in certain clinical contexts, such as during KRT, may positively impact fluid removal and prevent hypotension . NonetheDespite the comprehensive analysis provided in this study, it is essential to interpret the findings cautiously because of the varying methodological qualities of the included studies. This narrative rapid review has inherent limitations to consider. Firstly, its focus on the last five years of literature may exclude earlier valuable insights into albumin use in critical care, prioritizing recent developments but limiting historical context. Additionally, its non-systematic search, differing from PRISMA guidelines, may lead to omissions of relevant meta-analyses and systematic reviews, potentially introducing selection bias. Furthermore, relying on a single author for article selection could introduce subjectivity. Another limitation of this review is that it relied on the use of the term ‘meta-analysis’ as a filter in PubMed’s search criteria. While efforts were made to capture all relevant meta-analyses, it is acknowledged that the process of systematization by PubMed may result in some meta-analyses not being promptly marked as such, potentially leading to the omission of relevant studies. Lastly, the absence of PROSPERO registration means the review process, including search strategy and inclusion criteria, lacks pre-specification and public documentation. These limitations underscore the need for caution in interpreting these findings. The goal of this work is to offer a valuable synthesis of evidence within these constraints, recognizing that further research and systematic reviews may provide additional insights. Further high-quality research is warranted to confirm the association between HA use and the investigated outcomes in critically ill and perioperative patients. Clinicians should carefully consider the available evidence when making decisions regarding HA use in critically ill and perioperative patients.This rapid review presents a comprehensive analysis of recent meta-analyses that explored the use of HA in critically ill and perioperative patients. These findings highlight the heterogeneous effects of HA administration on various clinical outcomes and underscore the importance of considering methodological quality when interpreting evidence. While no significant impact on mortality was observed in critically ill patients, HA demonstrated potential benefits in reducing mortality in patients with septic shock. However, evidence from the context of cardiac surgery remains inconclusive. Combining HA with diuretics enhances diuresis and natriuresis, particularly in patients with diuretic resistance and hypoalbuminemia. Notably, no recent meta-analyses have investigated HA use in patients with hypoalbuminemia aiming for substitution, burns, or KRT. The utilization of HA in large-volume fluid resuscitation is supported by landmark studies, such as SAFE and ALBIOS, which documented its safety and hemodynamic superiority. While evidence suggests improved hemodynamic outcomes with HA, such as in hypoalbuminemic patients during mechanical ventilation with diuretics, further research is needed to confirm these findings. Moreover, the impact of HA on mortality in patients with TBI remains uncertain, with conflicting evidence. Therefore, clinicians should cautiously consider the available evidence when making decisions regarding the use of HA in critically ill and perioperative patients, recognizing the need for further high-quality research to better inform clinical practice in these settings.


The COVID-19 pandemic is a burden for the worldwide healthcare systems. Whereas a clear age-dependent mortality can be observed, especially multimorbid and frail persons are at an increased risk. As bio-functional rather than calendrical age is in the meanwhile known to play a crucial role for COVID-19-related outcomes, aging-associated risk factors, overall prognosis and physiological age-related changes should be systematically considered for clinical decision-making. In this overview, we focus on cellular senescence as a major factor of biological aging, associated with organ dysfunction and increased inflammation (inflammaging). Some main examples include age-related changes such as inflammaging and immunosenescence which appear to pave the way to SARS-CoV-2 pathogenicity mechanisms—the “cytokine storm”, the senescent endothelium which predisposes to the vascular manifestations of COVID-19, and the senile lung which impacts on COVID-19 diagnosis [cytokine storm can be sharply enhanced by the vascular hyperpermeability characteristic of the senescent endothelium. In turn, the cytokine storm can cause per se vascular hyperpermeability, which reveals particularly dangerous in the aged, already dysfunctional endothelium [As SARS-CoV-2 is detected in pneumocytes, less in macrophages and bronchiolar epithelial cells, and is associated with hemorrhagic necrosis and lymphocyte depletion in lymph nodes and spleen, lymphocytopenia  is displothelium .Age-related endothelial dysfunction with tendency to vessel rupture and multiorgan bleeding on one hand and thrombosis commonly observed in small vessels of severely ill COVID-19 patients in extrapulmonary organs free from coronavirus suggest alternative mechanisms beyond viral infection, such as hypoxemia and ischemia. These are also well-established age-related changes and hypoxemia-related cascades are associated with oxygen deficiency and increased generation of reactive oxygen species (ROS) occurring with increasing age , 13. As hallmarks of aging, one of the main drivers of COVID-19 lethality is senescence . Immunosenescence with low self-renewal capacity of specialized immune cells like lymphocytes and chronic low-grade inflammation might be a facilitating factor of SARS-CoV-2-induced pathogenicity [As mentioned above, among the genicity . Senescegenicity .Research in animal models and some initial data in humans suggest the hypothesis that the typical pro-inflammatory state of aging is in large part sustained by the accumulation of senescent cells and the spilling in the blood of SASP including cytokines and chemokines. Systemic, sustained low-grade chronic inflammation due to persistent tissue damage, environmental stressors, unhealthy lifestyle, and social and psychological stress represents a modular response of natural immunity and, indeed, is associated with the risk of developing many chronic diseases—insulin resistance, CVD, osteoarthritis, chronic obstructive pulmonary disease (COPD) and neurodegenerative processes—all characterized by the accumulation of senescent cells . DysfuncIn addition to inflammaging, garbaging, senescence and SASP, the individual’s history of exposure to certain microorganisms (eg. HIV and CMV) or antigens—immunobiography—may influence the degree and characteristic of the inflammatory response to various stimuli, SARS-Cov-2 lethality, inflammging itself and frailty. For instance, immunobiography may mediate the chronic inflammation and abnormal production of cytokines  as well as altered immune T-cell response characterizing metabolic syndrome and adiposity, in turn risk factors for poor outcomes during COVID-19 . SchmidtThese findings, facilitating the identification of proteins characteristic of senescence-associated phenotypes, may help the cataloging of potential senescence biomarkers to assess the burden, originating stimulus, and tissue of origin of senescent cells in vivo in COVID-19.http://ec.europa.eu). A key public health challenge is to ensure citizens remain healthy and disability-free for as long as possible, but the increase in life expectancy and global population aging in the past 50 years have resulted in substantial challenges to societies and health care systems. These have been maximized by COVID-19. Disability outweighs multimorbidity in regard to associations with adverse health outcomes in older adults, as its development is a multifactorial process that involves biopsychosocial factors. Frailty, which precedes disability and represents the transition between healthy and unhealthy states, has been well recognized as an age-related vulnerability resulting from impaired homeostasis, reduced physiological reserve and various stressors also related to biopsychosocial domains [In Europe, the number of older adults aged 60 years and over is set to double between 2002 and 2025, to reach a population of 1.2 billion in 2025, with fastest growth expected among those aged ≥ 85 years. Population projections suggest that the EU-27 old-age dependency ratio will continue to climb and will peak at 56.7% by 2050, when there will be fewer than two persons of working age for each older person. Accordingly, there will be half a million centenarians in the EU-27 by 2050 ( domains . Indepen domains , psychos domains –35. Frai domains , 36, the domains . While C


Cardiac rehabilitation (CR) improves outcomes in heart disease yet remains vastly underutilized. Remote CR enhanced with a digital health intervention (DHI) may offer higher access and improved patient-centered outcomes over non-technology approaches. We sought to pragmatically determine whether offering a DHI improves CR access, cardiac risk profile, and patient-reported outcome measures.Adults referred to CR at a tertiary VA medical center between October 2017 and December 2021 were offered enrollment into a DHI alongside other CR modalities using shared decision-making. The DHI consisted of remote CR with a structured, 3-month home exercise program enhanced with multi-component coaching, a commercial smartphone app, and wearable activity tracker. We measured completion rates among DHI participants and evaluated changes in 6-min walk distance, cardiovascular risk factors, and patient-reported outcomes from pre- to post-intervention.P < 0.01) and low-density lipoprotein cholesterol , and the absolute proportion of patients who reported smoking decreased  among DHI participants with available data. No adverse events were reported.Among 1,643 patients referred to CR, 258 (16%) consented to the DHI where the mean age was 60 ± 9 years, 93% were male, and 48% were black. A majority (90%) of the DHI group completed the program. Over 3-months, significant improvements were seen in 6MWT . Cardiac rehabilitation (CR) has been shown to reduce hospital readmissions, recurrent cardiovascular events, depression, and mortality, yet overall participation remains low . Fewer tDigital health interventions (DHI) that promote self-management can effectively deliver patient-centered cardiovascular prevention programs –13. WhenSmart HEART  is a comprehensive DHI for remote CR delivery that integrates mobile health technologies into home-based exercise training and lifestyle counseling. We previously reported the feasibility of Smart HEART in veterans demonstrating high engagement and patient satisfaction scores,  and haveIn this study, we describe the real-world impact of Smart HEART following implementation within a single Department of Veterans Affairs (VA) medical center. We used a pragmatic, open-label study design as a resource-efficient method to measure the impact of Smart HEART on CR access, measures of cardiovascular health, and patient-reported outcomes within routine clinical practice.The current analysis focuses on unique patients referred for CR between October 2017 and December 2021 at the Atlanta VA Medical Center, part of the Veterans Health Administration (VHA). Using a shared decision-making model that considered each patient’s preference, cardiac risk profile, and technology literacy, sequentially referred patients were offered enrollment into our facility’s remote CR program (either with or without the DHI-enhancements) in addition to enrollment into a traditional, center-based CR program at a non-VA facility through the VA Community Care Program. Enrollment in remote and center-based CR was not considered mutually exclusive to encourage patient choice, and patients were permitted to participate in both if they desired. We present data from the DHI program only, as data from the other CR programs were severely limited and outside of the scope of this study.The DHI components were developed by an industry partner  who was not involved in the study design but participated in training the study team and delivering parts of the DHI intervention, including direct patient coaching and data collection. All the patients provided informed consent before enrollment. The Institutional Review Board at Emory University and the Research & Development Committee at the Department of Veterans Affairs approved the study protocol. The study was registered with the U.S. National Library of Medicine ClinicalTrials.gov registry (NCT02791685) on 07/06/2016.Eligible patients were all adults aged 21 years or older referred to CR with a qualifying diagnosis per established criteria  . PatientMovn is a commercially available program for remote CR based on MULTIFIT, , 24 a caThe coach developed an exercise prescription tailored for each participant based on a target range for HR derived from a pre-enrollment 6-min walk test (6MWT) or using the rate of perceived exertion (RPE) based on the Borg scale  if baselDHI participants then received reminders to exercise via the Movn app, where they could also self-log exercise activity, vital signs, and medication adherence. The coach could passively monitor each participant’s data through an integrated online case-management dashboard provided by Movn. They could also send health-related surveys to each participant at the beginning of the program, each week, or at the completion of the DHI.The primary outcome was the overall rate of DHI enrollment and completion as a proportion of total CR referrals. Secondary outcomes included changes in clinical and patient-reported endpoints following successful completion of the 12-week DHI program, including the 6MWT; ; cardiovWe defined DHI completion as either 1) participation in a minimum of six (6) remote coaching visits  that were documented as care encounters in the medical record or 2) successful completion of a pre-planned exit visit for follow-up testing. Blinding was not considered feasible based on the nature of the intervention, which required active coordination between study team members and the industry collaborator.To measure DHI engagement, we calculated the total number of participants and the average number of usage days for various features of the Movn app that required active engagement by the patient, including logging of exercise sessions; self-measured BP, HR, weight, and medication adherence; and self-reported smoking status.p < 0.05. Analyses were performed using SAS Enterprise  and Python .Frequencies and percentages were used to summarize all categorical variables, including the primary outcome of DHI completion. Continuous variables were summarized with group means and standard deviations. For within-group comparisons of secondary outcomes, we performed paired t-tests and calculated 95% confidence intervals for all normally distributed data and Wilcoxon rank-sum for highly skewed data. Categorical data were compared using chi-square tests. Secondary outcomes were analyzed based on availability (including via chart review) and not DHI completion. The a priori level for statistical significance was a 2-sided Our facility received 1,653 unique, first-time CR referrals between October 2017 and December 2021  were seen in a post- vs. pre-intervention analysis among DHI participants with available data , average weekly step counts  total cholesterol (136 vs. 148 mg/dL), LDL-C (71 vs. 81 mg/dL), systolic (125 vs 129 mmHg) and diastolic (76 vs. 79 mmHg) BP, BMI (31.1 vs. 31.8) and smoking rates , health behaviors , functional status, and depressive symptoms. By adopting technology, veterans were able to benefit from improved monitoring and increased access to their provider, which is particularly important given the high level of morbidity and access barriers they otherwise may face with multiple chronic conditions, rurality, and low socioeconomic status .Digital health technologies are now used broadly across the consumer and healthcare delivery sectors , 30. IntTherefore, our study responds to this critical need for evidence by supporting the pragmatic implementation of patient-centered CR strategies that can be efficiently deployed in response to the rapidly shifting needs of patients and healthcare systems . Given tAlthough we did not present a control group due to limited data, our findings are in line with results from the literature on similar programs that health status improves in multiple domains after participation in structured exercise and risk reduction programs . As withSuccessful widescale adoption of DHIs into the full spectrum of CR delivery, including remote programs, depends on several factors. First, although the state of evidence continues to expand and support using digital technologies in more vulnerable populations with studies such as ours, a more robust framework for comprehensive and equity-centered digital health in CR is needed . Second,Our study has several limitations. All the participants were veterans and members of an integrated healthcare system consisting primarily of males, which limits its generalizability. Nonetheless, the cohort was racially diverse, as nearly half were Black. We also had limited power to analyze differences based on referral diagnosis, including ischemic  and non-ischemic  heart disease. Another limitation was the lack of a control group, which was in part due to limited data and the pragmatic nature of this study. As such, we focused primarily on factors like overall enrollment, which is impressive considering that normally less than 10% of eligible Veterans participate in CR. Nonetheless, veterans who were not comfortable with technology, who are often sicker and older, were not enrolled in the DHI. The coronavirus pandemic resulted in many canceled in-person data collection visits and missing data, highlighted in Table In conclusion, we found that remote CR with DHI was feasible in a VA hospital setting which serves many high-risk patients with low socioeconomic status, and also where many such studies are challenging to implement because of VA-specific privacy requirements. Health status of participants improved which was in line with other similar programs. Despite the challenges of implementing technology in such an environment, many veterans were able to engage on a daily basis, and completion rates were high. More research is needed to understand the potential role of this program at other centers and its potential impact on long-term outcomes such as mortality.


The identification of contributing factors leading to the development of Colorectal Cancer (CRC), as the third fatal malignancy, is crucial. Today, the tumor microenvironment has been shown to play a key role in CRC progression. Fibroblast-Activation Protein-α (FAP) is a type II transmembrane cell surface proteinase expressed on the surface of cancer-associated fibroblasts in tumor stroma. As an enzyme, FAP has di- and endoprolylpeptidase, endoprotease, and gelatinase/collagenase activities in the Tumor Microenvironment (TME). According to recent reports, FAP overexpression in CRC contributes to adverse clinical outcomes such as increased lymph node metastasis, tumor recurrence, and angiogenesis, as well as decreased overall survival. In this review, studies about the expression level of FAP and its associations with CRC patients' prognosis are reviewed. High expression levels of FAP and its association with clinicopathological factors have made as a potential target. In many studies, FAP has been evaluated as a therapeutic target and diagnostic factor into which the current review tries to provide a comprehensive insight.Video AbstractThe online version contains supplementary material available at 10.1186/s12964-023-01151-y. Annually, 900,000 deaths from Colorectal Cancer (CRC) are reported, and 1.8 million new patients are diagnosed with this cancer. The incidence of CRC is increasing gradually in the world and it is predicted that by 2035, the number of new cases will reach 2.5 million worldwide , GastroiRadical surgery or surgery followed by postoperative chemotherapy and radiotherapy are the primary therapeutic strategies for patients diagnosed at stages II and III , 10. HowIt has been demonstrated that Tumor Microenvironment (TME) or tumor stroma around solid tumors could be a proper platform for tumorigenesis and progression . The TMEOne of these cell types is CAFs . InteresAccording to the investigations, CAFs participate in tumorigenesis in different ways. They promote angiogenesis, increase proliferation and invasion, and suppress the immune system . There a. stated that this seems to be the main enzymatic role of FAP. Some investigations identified FAP’s endopeptidase activity substrates, including denatured type I collagen, α2-antiplasmin -Sibrotuzumab. No absorption in normal organs was reported suggesting that Sibrotuzumab was a safe antibody; however, the authors stated that the vaccine failed to elicit a proper anti-tumor response Ga-FAPI PET/Computed Tomography (CT) in different malignancies. Although this approach is not flawless, they reported a patient-based pooled sensitivity of 0.99  and a pooled specificity of 0.87  Ga-FAPI) showed intense uptake in different tumoral lesions and their metastases, including CRC , 136. So62–1.00) . Their r. reported that the target-to-background ratio of [68Ga]Ga-FAPI was higher than [18F]FDG, which may lead to better visualization per se and higher detection of smaller lesions, hypothetically. Additionally, they showed that the detection rate of [68Ga]Ga-FAPI PET/CT was equal to or higher than that of [18F]FDG PET/CT in different malignancies fluorodeoxyglucose ([18F]FDG) is the most widely accepted radioligand imaging in oncology. Hence, the diagnostic performance of any new tracer is compared to [18F]FDG. In a recent systematic review, Treglia et algnancies . Being sgnancies , and Ga-FAPI is the low background uptake in the liver and brain , 136 tha. compared the diagnostic performance of PET/CT imaging performed with (68)Ga-DOTA-FAPI and (18)FDG in detecting liver metastases in patients with gastrointestinal system cancer. They found that (68)Ga-DOTA-FAPI-PET/CT was superior over (18)FDG-PET/CT in the detection of liver metastases of GIS cancers, and it can be a complementary method, especially in negative cases with (18)FDG-PET/CT [The ultimate aim of imaging is accurate management. The effect of [68Ga]Ga-FAPI PET/CT in lower GI tract malignancies was evaluated compared to the standard imaging. (68)Ga-FAPI PET/CT was performed on a cohort of 22 patients with LGT tumors, including 15 patients with metastatic disease, one with suspected local relapse, and six treatment-naïve patients. Uptake of (68)Ga-FAPI-04 and (68)Ga-FAPI-46 was quantified by SUV(max) and SUV(mean) after comparison with standard imaging. The highest uptake of FAPI tracer was observed in liver metastases and anal cancer, with an SUV(max) of 9.1 and 13.9, respectively. Because of low background activity in normal tissue, most lesions had a high tumor-to-background ratio of more than 3. Nothing was found in 47% of the patients (10/21), and the management significantly altered in 19% (4/21) . The preG-PET/CT .Non-specific uptake of [68Ga]Ga-FAPI is its main demerit. Except for tumors with significant expression of FAP, [68Ga]Ga-FAPI is accumulated in many other conditions, such as inflammatory processes , 140–142There is an interest in radioligand therapy whenever a radiotracer successfully captures tumoral lesions. Radioligand therapy is usually considered when other standard treatments become ineffective. A limited number of studies about FAPI-based radioligand therapy are found in the literature review. Some therapeutic radionuclides, such as Copper-64 and Actinium-225, have been successfully labeled with FAPI, showing tumor-specific uptake . In the The main challenge of FAPI-based radioligand therapy is its efflux from the malignant cells . Using sIn summary, FAPI-based molecular imaging provides valuable information on FAP expression in different malignancies, including CRC. Preliminary studies suggest that [68Ga]Ga-FAPI PET/CT enjoys high diagnostic performance than the current standard methods. Future studies should further clarify its role in staging and re-staging settings, prediction of prognosis, and effect on management. Moreover, FAPI-based radioligand therapy in advanced CRC patients is another intriguing aspect of targeted therapy, which is worth to be addressed in the following investigations.Concluding from the evidence and findings gained from the studies about the expression of FAP in CRC tumor samples and its association with prognosis. It can be said that high expression of FAP in CRC stroma increases angiogenesis, and collagen degradation in the tumor stroma elevates the rate of lymph node and liver metastasis and also increases disease recurrence. It also suppresses the immune system in the CRC microenvironment. FAP overexpression in CRC stroma is associated with poor patient overall survival and prognosis.Despite many efforts to determine the extent of FAP expression and its association with the prognosis of CRC, there are still issues that need to be addressed in future studies. For instance, the association between FAP expression and patients' responses to radiotherapy and chemotherapy should be uncovered. Further studies are needed to investigate the association between tumoral site, age, smoking, and the patient's genetic history with FAP expression. Other studies could evaluate the role of FAP expression on the expression of other CAF markers, such as alpha-SMA, and elucidate the synergistic effect of these markers on prognosis in CRC. Moreover, measuring the expression of FAP in lymphatic and hepatic metastases samples help these types of metastases to be treated by targeting FAP in the future.+ T cells into the TME, and reduces tumor growth. Altogether, the application of DNA vaccines against FAP in CRC is a promising approach needed to be more addressed in the future to clarify their clinical function and toxicity better. Regarding monoclonal antibodies, first, Sibrotuzumab was used to target FAP in CRC and did not bring promising clinical outcomes. Another study showed that a monoclonal antibody named RG7386, capable of simultaneously targeting FAP and DR5, had significant anti-tumor activities. This study confirmed that if properly designed, monoclonal antibodies could be promising nominees for targeting FAP in CRC; however, further studies are needed for more clarification.Considering FAP targeting in CRC, inhibiting FAP’s enzymatic activity with Talabostat does not bring an acceptable outcome in CRC treatment. However, prodrug BF211-03, a substrate for FAP, has shown good anti-tumor properties and low normal tissue toxicity. In immunotherapy with DNA vaccines, in vivo studies showed that vaccination against FAP triggers the host's immune response against the tumor, increases the penetration of CD8FAP does not overexpress in all CRC patients; therefore, the decision to utilize appropriate therapies must be according to an initial assessment of FAP expression in each patient. In addition, FAP may express in non-tumor tissues such as wound healing sites, which makes it vital not to select a type of treatment that could affect the wound healing process.Regarding FAP theranostic implications, FAPI-based molecular imaging provides helpful information about FAP expression in different malignancies, including CRC. previous studies suggest that [68Ga]Ga-FAPI PET/CT has higher diagnostic performance than the current standard methods. Future studies should clarify its role in staging and re-staging settings, prediction of prognosis, and effect on management. Moreover, FAPI-based radioligand therapy in advanced CRC patients is another intriguing aspect of targeted therapy, which is worth to be addressed in the following investigations.


Early disease diagnosis is critical for better management and treatment outcome of patients. Therefore, diagnostic methods should ideally be accurate, consistent, easy to perform at low cost and preferably non-invasive. In recent years, various biomarkers have been studied for the detection of cardiovascular diseases, cerebrovascular diseases, infectious diseases, diabetes mellitus and malignancies. Exosomal microRNA (miRNA) are small non-coding RNA molecules that influence gene expression after transcription. Previous studies have shown that these types of miRNAs can potentially be used as biomarkers for cancers of the breast and colon, as well as diffuse large B-cell lymphoma. It may also be used to indicate viral and bacterial infections, such as the human immunodeficiency virus (HIV), tuberculosis and hepatitis. However, its use in the diagnosis of vector-borne diseases is rather limited. Therefore, this review aims to introduce several miRNAs derived from exosomal plasma that may potentially serve as a disease biomarker due to the body’s immune response, with special focus on the early detection of vector-borne diseases. Plasmodium vivax, a rise in the level of plasma-derived microvesicles has been observed in the blood of patients, which potentially allows disease detection at an earlier stage (Extracellular vesicles (EVs) are a heterogeneous group of membrane vesicles secreted by nearly all cell types in normal physiology, and the secretion of their content is influenced by the cells’ current pathophysiological state . They arer stage . Apoptoter stage . A recener stage .Exosomes are nanometer-sized (50–150 nm) intraluminal vesicles (ILV) of multivesicular bodies (MVB) secreted by various cells, including the microglia . They haInfection by a vector-borne disease will trigger the effects of a host-parasite interaction, which facilitates the parasite’s long-term survival in the host body . The hosRecently, exosomes have gained much research attention in biomarker development as they contain specific proteins, microRNAs (miRNAs) and signaling molecules that are associated with disease progression . ExosomeArticle search and data collection were performed on PubMed, Google Scholar, and World Health Organization (WHO) databases. It included peer-reviewed articles with original data from 2010 to 2022. Non-peer-reviewed articles, conference abstracts, letters, articles without full-text were excluded. All articles were collected and compiled using the Mendeley application to eliminate duplicates. A PubMed database search using the keywords “extracellular vesicles and vector bore diseases” resulted in a total of 225 articles. After subsequently applying the keywords “exosomes and vector-borne disease,” a total of 115 articles were produced. As the search was narrowed down with the keywords “miRNA biomarker and vector bore diseases,” the articles were further reduced to 79. Finally, 31 articles remained when the second parameter “plasma miRNA and vector-borne diseases” was added. The articles were manually divided into two groups: “original articles” and “others” . The original articles addressing plasma exosome miRNA and vector-borne diseases became the focus of the study and were used as material in this review.Exosomes are critical paracrine mediators that may be detected in bodily fluids, including plasma . The conMiRNA are naturally occurring short non-coding RNA molecules with a length of about 21–25 nucleotides . MiRNA fDuring the early stage of human immunodeficiency virus-1 (HIV-1) infection, changes in exosomal miR-155 expression play a role in the development of an effective antiviral effector response by CD8 T cells and at the same time increase the number of regulatory T cells . Thus, eMost recently, reverse-transcription polymerase chain reaction (RT-PCR) has been mainly used to confirm COVID-19 infection. However, false-negatives may occur in a small percentage of tests due to a low viral load in patient samples . The useFrom DNA sequences, miRNAs are translated into precursor miRNAs (pre-miRNAs), mature miRNAs and primary miRNAs (pri-miRNAs). MiRNAs regulate protein translation by binding to the 3’ untranslated regions of mRNA template . HoweverBacteroides Fragilis (ETBF) is an enterotoxin-producing bacterium that is strongly associated with inflammatory bowel disease (IBD), colitis-associated colorectal cancer and colorectal cancer (CRC) as it has been observed to change the mucosal immune response and induce epithelial cell changes (Enterotoxigenic  changes . A recen changes . Plasma- changes .FOXP4 and EZH2 oncogenes (Ppm1f (Medulloblastoma (MB) is a malignant brain tumor that commonly affects children. Exosomal miR-101-3p and miR-423-5p from plasma of MB patients have been identified to act as tumor suppressors by directly targeting ncogenes . This shs  in host cells   could function as a biomarker for lymphatic filariasis disease  . The res disease . Table 3Flavivirus of the family Flaviviridae. This virus has a common size of between 40 and 65 nm and contains a positive single-stranded RNA genome , the Australian tick typhus , Rocky Mountain spotted fever , rickettsialpox , oriental spotted fever  and African tick bite fever . To accurately diagnose and treat these diseases, it is crucial to understand both the typical symptoms and epidemiology of a specific area   . More thre bugs) . Chagas re bugs) . The sigre bugs) . Plasma re bugs) .Schistosoma  is a mosquito-borne virus transmitted by material . Conventmaterial .Aedes aegypti and Aedes albopictus mosquitoes using RT-PCR in São Paulo, Brazil, has helped to understand the transmission dynamics of ZIKV and potential risk of future outbreaks in several neighborhoods in the city  is a mosquito-borne disease transmitted by Culex mosquitoes. Like dengue, West Nile, Yellow Fever and Zika counterparts, it is part of the family Flaviviridae that causes viral encephalitis . ConventAedes and some Culex mosquitoes. It is a positive-sense, single-stranded RNA virus in the family Togaviridae that causes Chikungunya disease (Chikungunya virus (CHIKV) is an alphavirus transmitted by  disease . Convent disease . Since tWuchereria bancrofti, Brugia malayi, and Brugia timori  is a mosquito-borne tropical disease caused by parasitic nematodes, such as a timori . These pnfection . The parelopment .Leishmania donovani in arthropod Phlebotomus argentipes using DNA amplification (PCR) and sequencing methods help to study the disease epidemiology in Kurunegala District, Sri Lanka  and serological tests, such as an indirect IFA, ELISA, and Western blot . The exori Lanka . The parri Lanka .The currently available diagnostic methods for many vector-borne diseases are insufficient and have many limitations. Most of the detection is dependent on the existence of signs and symptoms, or antibodies of particular pathogen. Therefore, there is an urgent need to support the development of new biomarker techniques in diagnostic platforms. Plasma-derived exosome miRNAs are more stable, reliable and highly concentrated than any other bodily fluids. Recent studies have indicated that exosomal miRNA within excretory-secretory products may serve as a route for successfully mediating parasite-host contacts for host manipulation. Interestingly, previous studies discovered certain differentially expressed host plasma-derived exosome miRNAs that may be potential diagnostic and prognostic biomarker of vector-borne diseases. However, there is still limited research of plasma exosome in vector-borne diseases as compared with other diseases such as malignancy. The lack of consistent definitions and a standard method causes considerable confusion in the laboratory study of exosomes. We believe that further research in this area will solve the problem, and provide the new ideas and approaches for the application of plasma-derived exosome miRNA in clinical practice.GV conducted the literature search and drafted the manuscript. WS conceived the idea of this review and gathered the data. WNS, SI, and AM gave critical ideas in drafting the manuscript. All authors approved the final submission of this manuscript.


The association between mammographic density (MD) and breast cancer (BC) recurrence and survival remains unclear. Patients receiving neoadjuvant chemotherapy (NACT) are in a vulnerable situation with the tumor within the breast during treatment. This study evaluated the association between MD and recurrence/survival in BC patients treated with NACT.th Edition) and recurrence-free/BC-specific survival at follow-up (Q1 2022) were addressed. Hazard ratios (HRs) for recurrence/BC-specific survival (BI-RADS a/b/c vs. d) were estimated using Cox regression analysis and adjusted for age, estrogen receptor status, human epidermal growth factor receptor 2 status, axillary lymph node status, tumor size, and complete pathological response.Patients with BC treated with NACT in Sweden (2005–2016) were retrospectively included (N=302). Associations between MD (Breast Imaging-Reporting and Data System (BI-RADS) 5A total of 86 recurrences and 64 deaths were recorded. The adjusted models showed that patients with BI-RADS d vs. BI-RADS a/b/c had an increased risk of recurrence  0.98–3.92)) and an increased risk of BC-specific death (HR 2.94 (95% CI 1.43–6.06)).These findings raise questions regarding personalized follow-up for BC patients with extremely dense breasts (BI-RADS d) pre-NACT. More extensive studies are required to confirm our findings. RecurreMammographic density (MD) is determined based on the amount of radiopaque breast parenchyma in the mammogram and describes the relationship between the white dense breast tissue and dark transparent fatty tissue . MD is eMD varies throughout life but declines with age, with the biggest drop occurring during the shift to menopause . Low MD in vivo  and BC recurrence and BC-specific survival in a retrospective cohort of patients treated with NACT, concomitant to generate more information about treatment response and prognosis.2Female BC patients treated with NACT in Sweden from 2005-2016 .Our results indicate that patients with heterogeneously dense MD (BI-RADS category c) might have marginally better recurrence-free and BC-specific survival following NACT than patients with non-dense breasts (BI-RADS category a/b). This was not observed in other studies, which tended to merge breast densities into two groups. For instance, in the previously mentioned study by Elsamany et al. , the two4.4In this study, we observed that patients with extremely dense breasts (BI-RADS d) had shorter BC-specific survival. If our results were to be confirmed in larger studies, MD could be used to identify patients who might benefit from additional treatment with NACT and patients who would need intensified follow-up with the goal of possibly preventing recurrence. This could lead to more personalized treatment regimens, reduced risk of recurrence, and improved patient survival. Moreover, it may be possible to de-escalate treatment for patients with less dense breasts and to avoid unnecessary complications from overtreatment with chemotherapy. In addition to MD, as either a categorical or continuous measure, the range of imaging biomarkers associated with BC risk in mammography, breast tomosynthesis, MRI, and ultrasound would be interesting to explore in the NACT setting .4.5One radiologist blindly assessed the MD, and only two people reviewed the medical charts, thus minimizing the risk of information bias. The BI-RADS distribution in this study was similar to that of the Western world, where minorities of women have the most (BI-RADS d) and least dense (BI-RADS a) breasts, respectively , as the In the cohort, only 16 and 26 patients were found in BI-RADS groups a and d, respectively, resulting in few events in these groups. However, our results suggest strong associations despite the small sample size. We adjusted for tumor biomarkers, such as hormone receptors; however, because of the small sample size, no subgroup analyses were performed according to molecular BC subtypes. Despite these limitations, we believe these findings will be of great clinical value for further investigation.In this observational study, pre-NACT MRI was not a clinical routine and was therefore not performed. We acknowledge the possibility of additional sites of malignancy not being identified before NACT in patients with extremely dense MD. However, in this study, >90% of patients with extremely dense MD underwent mastectomies, thus limiting this potential source of bias in our study. In this cohort, only pre-NACT MD was assessed.Addressing longitudinal changes in MD assessed using BI-RADS, in both pre- and postmenopausal women undergoing consecutive mammographic screenings, an increase in MD augmented future BC risk, whereas a decrease in MD was associated with a lower risk . A poten5Patients with the extremely dense breasts (BI-RADS d) were observed to have poorer recurrence-free and BC-specific survival than those with less dense breasts. This raises questions regarding individualized follow-up for women with BC with high-density breasts treated with NACT. More extensive studies are needed to confirm our findings before clinical implementation.The datasets presented in this article are not readily available because of privacy or ethical restrictions. Requests to access the datasets should be directed to ida.skarping@med.lu.se.The studies involving human participants were reviewed and approved by The Regional Ethics Committee of Lund, Sweden (Committee reference No.: 2014/13 and 2016/521). Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.AZ collected recurrence/survival data from medical charts, performed statistical survival analyses under supervision, critically interpreted data and results, and drafted the manuscript. HS participated in data interpretation and revised the manuscript. MF participated in data interpretation and revised the manuscript. IS is the principal contributor to this study. IS collected baseline data from medical charts, performed statistical descriptive analyses, supervised the statistical survival analyses, critically interpreted the data and results, drafted the manuscript, and organized its revision. All authors contributed to the article and approved the submitted version.


This study aimed to compare the effects of cognitive functional therapy (CFT) and movement system impairment (MSI)-based treatment on pain intensity, disability, Kinesiophobia, and gait kinetics in patients with chronic non-specific low back pain (CNSLBP).In a single-blind randomized clinical trial, we randomly assigned 91 patients with CNSLBP into CFT (n = 45) and MSI-based treatment (n = 46) groups. An 8-week training intervention was given to both groups. The researchers measured the primary outcome, which was pain intensity , and the secondary outcomes, including disability (Oswestry disability index), Kinesiophobia , and vertical ground reaction force (VGRF) parameters at self-selected and faster speed (Force distributor treadmill). We evaluated patients at baseline, at the end of the 8-week intervention (post-treatment), and six months after the first treatment. We used mixed-model ANOVA to evaluate the effects of the interaction between time (baseline vs. post-treatment vs. six-month follow-up) and group (CFT vs. MSI-based treatment) on each measure.CFT showed superiority over MSI-based treatment in reducing pain intensity  = 2.41), ODI , and Kinesiophobia  at eight weeks. The CFT also produced greater improvement in VGRF parameters, at both self-selected , and faster speed, FPF, WAR, POR] than the MSI, except SPF at eight weeks.This study suggests that the CFT is associated with better results in clinical and cognitive characteristics than the MSI-based treatment for CNSLBP, and the researchers maintained the treatment effects at six-month follow-up. Also, This study achieved better improvements in gait kinetics in CFT. CTF seems to be an appropriate and applicable treatment in clinical setting.https://www.umin.ac.jp/ with identifier number (UMIN000047455).The researchers retrospectively registered the trial 10/11/2022, at The online version contains supplementary material available at 10.1186/s12891-023-06815-x. Low back pain (LBP) affects people around the world at a high occurrence rate . ChronicOne important impairment in patients with LBP is related to the walking task. Pain, kinesiophobia, and effort to reduce pain by restricting spinal movement cause changes in gait parameters such as decreased step length and step speed, along with widened step width in patients with chronic LBP . The infCurrent management of chronic LBP includes a range of different treatments –9. Over A movement-based strategy, uniquely designed for each patient, suggests that the MSI-based treatment approach improves the accuracy of spinal movements and induces specific changes in the musculoskeletal system, such as altering movement patterns and promoting painless movement patterns , 15. In On the other hand, CFT is a novel approach that not only cover postural and movement behaviors, but also consists of two other components includes biopsychosocial understanding of pain, and lifestyle change . To addrAccording to the above-mentioned statements, this RCT aimed to compare the MSI-based treatment with the CFT approach on pain intensity, disability, Kinesiophobia, and gait kinetics in patients with CNSLBP. We hypothesized that CFT could improve pain, disability, and Kinesiophobia, while MSI-based treatment seemed more influential for gait kinetics.https://www.umin.ac.jp/ with identifier number (UMIN000047455).This was a 2-arm RCT, parallel-group study with blind outcomes assessor, conducted from September 2018 to August 2019 in the corrective exercises center of the Kharazmi University, Tehran, Iran. The trial was retrospective registered 10/11/2022, at The researchers measured pain intensity as the primary outcome using the Numeric Ratings Scale (NRS) and assessed changes in disability, Kinesiophobia, and VGRF parameters as secondary outcomes with the Oswestry Disability Index (ODI), Tampa Kinesiophobia Scale (TKI), and (Force distributor treadmill), respectively, a week before the interventions. After assessing demographic data and outcome measures, the researchers randomly assigned patients to receive either CFT or MSI-based treatment.The biomechanics laboratory of the Sport Sciences Research Institute conducted baseline, post-treatment, and follow-up assessments. A well-experienced assessor assessed the outcomes at the baseline, the end of the 8-week training period (post-treatment), and the end of the six-month follow-up in the same place. The patients did not receive any treatment, including physiotherapy and exercise, between the post-treatment and the six-month follow-up. The supervised clinical sessions in the corrective exercises center of the university also performed the treatments.The patients complained LBP were recruited through flyers in the physical therapy clinics, occupational health services, and primary care practices. Based on the inclusion criteria, the researchers enrolled eligible patients to participate in the study.https://icd.who.int/)), classified by the duration of pain for more than 12 weeks (Non-specific LBP) [This study included patients with LBP  and overIf the researchers found neurological disorders, spinal pathologies, structural deformity, osteoporosis, inflammatory disorder , radicular syndrome, history of tumor and fracture in the spine, true leg length discrepancy more than 20 mm, or BMI greater than 30 kg/m2, they excluded the patients.Based on previous studies, researchers calculated that they should enroll at least 40 subjects per each group to complete the study if they used an α error of 0.05, standard deviation of 2.5, and a power of 0.8 , 22. Thehttp://randomizer.org. The researcher arranged the allocation sequence using a blocked randomization model with a block size of 4 and concealed it in numbered, sealed, opaque envelopes. Just before the first treatment session, the treating clinicians opened the envelope to reveal the group allocation.A researcher with no involvement in the trial conducted randomization based on a computer-generated random sequencing  using the website The researchers measured pain intensity using a numerical rating scale (0–10), where 0 signified no pain, and 10 represented the worst unbearable pain. The patients rated their current level of pain intensity using this scale. The numeric rating scale version used to measure pain intensity has not been cross-culturally adapted for the Persian-speaking population with low back pain. Although the NRS is a widely accepted and validated tool for evaluating self-reported pain intensity in various populations . ResearcThis study used the Persian translated Oswestry Disability Index to assess disability in patients with low back pain. It is important to note that the researchers cross-culturally adapted the Oswestry Disability Index version for Persian-speaking patients with LBP in this study . This adOne study used the Persian translation of Tampa Scale for Kinesiophobia to evaluate kinesiophobia. This specific version has been cross-culturally adapted for the Iranian patients with chronic persistent pain . This coBased on the study of da Fonseca et al. (2009) we assessed VGRF parameters . After iFirst (FPF) and second Peak Force (SPF): the first and second maximum peak of VGRF during the stance phase in straight walking after the heel contact. Mid-Support Force (MSF): the minimum peak of VGRF between the first and second peak forces. Weight Acceptance Rate (WAR): the magnitude of the first peak force divided by the time at which it occurred. Push-Off Rate (POR): the magnitude of the second peak force divided by the time from the second peak force until the end of the stance phase .The movement system impairment-based treatment group received 11 sessions of MSI-based treatment over the 8 weeks for 60 min per session with a supervision of a native speaker experienced above 5 years) physical therapist with the knowledge of MSI-based treatment . The res years phCognitive functional therapy was prescribed for each patient in CFT group based the CFT protocol conducted by O’Sullivan et al. 2015) , 33. Pat5 , 33. PA statistician performed statistical analyses, using SPSS version 16.0 . The Kolmogorov-Smirnov and Levene tests were used to check the normal distribution of variables and homogeneity of variance, respectively. We used mixed-model ANOVA to evaluate the effects of the interaction between time (baseline vs. post-treatment vs. 6-month follow-up) and group (CFT vs. MSI) on each measure. We used Bonferroni correction to assess changes in each group across the three-time points. For each variable, we calculated the percentage of change compared with baseline. We also conducted intention-to-treat analyses for all randomized patients, including those who dropped out. Cohen’s d was used to calculate effect sizes (ES), which were classified as small (d < 0.20), medium (d = 0.21–0.79), or large (d > 0.80) .The CONSORT 2010 guidelines display the flow diagram of this trial in Fig. F = 117.29, p < 0.001), ODI  and TSK . Between groups analysis showed significant differences at 8-weeks post-intervention  also the values were significantly lower in NRS, ODI and TSK in the CFT group. At 6-months follow-up there was a statistically significant difference , where the values were significantly lower in NRS, ODI and TSK in the CFT group . These results suggest that the CFT protocol was more effective than MSI in reducing pain intensity, disability, and kinesiophobia. The mean of changes in for NRS, ODI, and TSK in both group were more than MCIDs, except for ODI in the follow up. However, in the group of CFT, thses changes were higher as follow: NRS , ODI , and TSK .Table self−selected speed, SPF self−selected speed, MSF self−selected speed, WAR self−selected speed, POR self−selected speed, FPF faster speed, WAR faster speed, and POR faster speed showed significant group × time interaction effects. Bonferroni post hoc analysis showed higher scores in the CFT group on the GRF parameters at self-selected speed and GRF parameters at faster speed at 8 weeks’ post-intervention, and 6 months follow-up. No statistically significant interaction between interventions was.Table The CFT and MSI treatment groups did not report any adverse events during the eight-week training, and the assessments in the pre-test, post-test, and 6-month follow-up did not record any adverse events.This study aimed to compare efficacy of CFT and MSI-based treatment on pain, disability, kinesiophobia, and gait kinetics in CNSLBP patients. Evaluation of functional status revealed superiority of CFT approach on reduction in pain intensity, disability, and kinesiophobia through an 8-week intervention and six months follow up over MSI-based treatment.According to the bio-psycho-physiological improvement in recent years, it is time for health-care practitioners to shift their perspective away from a biomedical model, toward prescribing the treatment for CNSLBP based on a multidimensional classification-based approach with the aim of making the treatment more self-centered and focusing on cognitive-behavioral aspects rather than the signs and symptoms associated with the disorder.According to O’Sullivan’s classification, two sensitizations found LBP, including central sensitization affected by psychological and cognitive factors, and peripheral sensitization connected to impairments in movement and controlling movement . CFT in Activity avoidance is related to fear, which reflects the belief that activity may result in (re)injury or increased pain as a result of dysfunctional interpretations of pain and injury that can be adaptive in the acute pain stage but contradictorily worsen the problem in the case of chronic pain . The useTo support our results, Vibe Fersum et al. (2013)  stated tAfter 8 weeks of treatment with both interventions, the evaluation of gait kinetics in people with CNSLBP showed significant improvements in VGRF parameters such as FPF, SPF, MSF, WAR, and POR from baseline. However, the CFT approach appeared to be more effective than the MSI-based treatment. The results showed that, the POR and WAR increased in the self-selected speed in both treatment groups. It means that the time to reach heel-contact and return time from push off have decreased . Thus, iAt the self-selected and fastest walking speeds, WAR and POR increased in the CFT group more than in the MSI group, representing increased speed and decreased time in reaching the FPF peak and returning from the SPF peak. FPF and SPF both increased at the fastest walking speeds in both intervention groups. Generally, more improvement in MSF was observed in the CFT group. To the best of our knowledge, this is the first trial assessing the effects of CFT and MSI-based treatment on gait kinetics in patients with CNSLBP. Our results clearly showed that impaired gait in CNSLBP patients improved more in the CFT group than in the MSI group.Previously, Barzilay et al. (2016)  found thTo support Barzilay’s study findings, we found the improvement of VGRF parameters with the improvement of pain, disability, and kinesiophobia. In CFT group we saw significant percentage of changes for pain (60.74%), disability (52.98%), and kinesiophonbia (44.6%) accompanied with the better improvement of VGRF parameters after prescribing eight-week multidimensional intervention. Also, significant percentage of changes for pain (44.23%), disability (50.15%), kinesiophonbia (36.73%) and improvement of VGRF parameters observed in CFT group six months after the first treatment.According to Krekoukias et.al , LBP patIn this study patients in both experimental groups preferred to walk faster in post-test in both self-selected speed and faster speed, besides the push-off rate improved in both groups specially in CFT group. Therefore, it is likely cognitive functional therapy improved the dealing with perturbations and as a result progressed the push-off rate and gait speed.Patients with low back pain, showing higher electromyographic activity of the rectus abdominis and erector spinae during gait . Also, bIn contrast to the physiological gait, the pelvis rotates in the opposite direction from the trunk, but low back pain patients demonstrated gait compensations that exhibit increased pelvic rotation with concurrent trunk rotation which is assumed for antalgic purposes .In this study, the CFT group showed better pain improvement compared to the MSI group, which may result in a greater reduction of these compensatory movements. The CFT group has demonstrated more progression in gait parameters.Other aspects include the influence doctors have on patient outcomes and treatment confirmation, including their communication skills, empathy and degree of trust . Along wsimilar to our previous hypothesis, we can draw a conclusion that when patients received both psychological- and movement-based treatment that educated patients how to move better in their daily-routines, overcome their fear and change their beliefs toward a self-control management, they can perform better their functional tasks like walking with less fear of movement.This study has some limitations First, to better evaluate gait performance, researchers propose including not only VGRF but also the horizontal ground reaction forces. Second, the current study is limited by the lack of electromyography (EMG) in recording the functioning of core and abdominal muscles. Third, future studies should examine CFT intervention with other therapeutic methods, as it is currently compared with MSI treatment in this study. Fourth, this study based its sampling strategy on patients with chronic low back pain, which is defined as pain lasting for 90 days or more. Although the researchers selected pain intensity as the primary outcome measure, it should be noted that experts often recommend studies of patients with chronic pain to prioritize the primary outcome of disability, as pain intensity is more susceptible to regression to the mean. Despite using validated measurement tools and baseline assessments to minimize this potential limitation, the decision to make pain intensity the primary outcome may influence the overall interpretation of treatment efficacy. Finally, the lack of a translated and validated Persian version of Central Sensitization Inventory prevented us from assessing central sensitization. If we had used this tool, we could have determined whether there was any association between pain improvement and central sensitization in the studied population. For future similar studies, a translated and validated version of the Persian Central Sensitization Inventory will be beneficial, in addition to other pain intensity measures. For future studies, authors also suggest that random forest analysis with the Shapley Additive Explanations (SHAP) summary plot can present useful information regarding the rankings of major predictors and the directions of their associations with the superior effects of cognitive functional therapy.The main implication of the current findings is that, in addition to changing lifestyle and functional training, fostering a biopsychosocial understanding of pain and cognitive training are helpful for maximizing efficiency of treatment in patients with non-specific chronic LBP. The current data suggest that both CFT and MSI-based treatment seem to have beneficial effects on rehabilitation of CNSLBP patients through reduction of pain, disability, and fear-avoidance behaviors, and improvement of VGRF parameters. The CFT approach produces better outcomes, which may be due to its multidimensional therapeutic effect. Of course, the results of this study need to be confirmed with a larger number of patients.Below is the link to the electronic supplementary material.Supplementary Material 1Supplementary Material 2


HLA-C (human leukocyte antigen C) gene, were found to be differentially expressed in skin. The allele frequencies for rs2074494 and rs5010528 also appear to significantly differ across continents. We highlight the utility of these population-specific HLA-C genetic variants for genetic association studies, and aid in early prognosis and disease treatment of SJS.Stevens-Johnson syndrome (SJS) produces a severe hypersensitivity reaction caused by Herpes simplex virus or mycoplasma infection, vaccination, systemic disease, or other agents. Several studies have investigated the genetic susceptibility involved in SJS. To provide further genetic insights into the pathogenesis of SJS, this study prioritized high-impact, SJS-associated pathogenic variants through integrating bioinformatic and population genetic data. First, we identified SJS-associated single nucleotide polymorphisms from the genome-wide association studies catalog, followed by genome annotation with HaploReg and variant validation with Ensembl. Subsequently, expression quantitative trait locus analysis (eQTL) from GTEx identified human genetic variants with differential gene expression across human tissues. Our results indicate that two variants, namely rs2074494 and rs5010528, which are encoded by the  Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are potentially life-threatening diseases . In partSJS/TEN is widespread in the mucocutaneous immune region, causing exfoliation of the skin on the mucosal surface . The incTherefore, primary prevention is the best mitigation for SJS. SJS is categorized as a severe cutaneous adverse reaction (SCAR), and several drugs have been implicated in disease pathogenesis. Non-steroidal anti-inflammatory drugs and other multi-ingredient formulations are widely used to relieve the symptoms. Several studies are reporting adverse skin drug reactions that are often SJS-associated with severe ocular complications . Preventhttp://www.ebi.ac.uk/gwas accessed December 19, 2022). SJS associated with 74 single nucleotide polymorphisms (SNPs) were obtained and further analysis was carried out using HaploReg (version 4.1). Further analysis yielded a total of 41 SNPs with a significance value of p-value < 10-8. This value is used to account for several tests in the GWAS catalog. These values are widely used to identify associations between variants and shared genetic traits with adjacent gene expression [http://www.gtexportal.org/home/ accessed December 19, 2022), which was found by gene expression from various networks. The HLA-C (human leukocyte antigen C) genetic variant is present in human skin and tissue (lower extremities) exposed to sunlight obtained from the GTEx Portal database. Then confirm the variant using the Ensembl Genome Browser . Furthermore, the allele frequencies of variants associated SJS were evaluated in different populations including African, American, East Asian, European, and Southeast Asian populations. Samples from each region consisted of 331 individuals (Africa), 199 individuals (America), 247 individuals (East Asia), and 136 individuals (Southeast Asia). Then, to find out the function of the various gene variants, an evaluation was carried out using the SNP Nexus database .Genomic information not only can be leveraged to identify the variant-associated disease, but it can also be translated into actionable knowledge for the disease. SJS is one of the severe skin reaction due to genomic risk factors. In this study, we used a bioinformatic-based approach to prioritize the pathogenic variants that potentially trigger the SJS. Detailed information regarding the study design has been depicted in pression . Further-8. Based on the findings presented in We first identified SNPs associated with SJS from the GWAS database, resulting in 74 SNPs associated with SJS. We identified 41 unique SNPs associated with SJS after removing all SNPs duplication . Based oHLA-C genes were prioritized as the biological risk SNPs for SJS. SJS is characterized by necrosis and shedding of the epidermis, known as the triad of disorders of the vesiculobullous skin, orifice mucosa, and eyes, accompanied by severe general symptoms [HLA-C gene has an important role in protecting against cancer and viruses. However, the HLA-C gene may also be involved in allograft rejection, the state of preeclampsia, and is also present in autoimmune diseases [Through our integrative bioinformatics approach, two variants with a missense mutation  that encoded the symptoms . It was diseases . The diadiseases .HLA-C gene expression in human tissues, we used the GTEx Portal database , which contains gene expression levels in various tissues. eQTL annotation comprises the most apparent functional consequences of genetic variation. Whole blood, spleen, lung, and lymphocyte cells demonstrate the highest HLA-C gene expression across the 16 human tissues analyzed from GTEx in To evaluate HLA-A, HLA-B, and HLA-C, have been reported as the loci most strongly associated with susceptibility to all types of SJS and TEN, including cold medicine-related (CM-SJS) and TEN with severe ocular complications (SOC). Although non-synonymous substitutions affecting peptide binding or HLA molecular conformation have been considered significant factors in the pathogenesis of immunological diseases, indeed, different HLA-C expression levels have been reported for the different alleles, with higher HLA-C expression leading to increased Tc (Trypanosoma cruzi) responses and adverse effects in Crohn's disease. It was also reported that genetic variation in HLA-A and other autosomal genes has been identified as a risk factor for SJS/TEN associated with flu drugs with SOC such as CM-SJS or TEN with SOC [Human leukocyte antigen (HLA) class I genes, including with SOC .HLA-A and TLR3 [HLA-A and REC14-32, and HLA-A and PTGER3 [When individuals with a genetic background containing SJS/TEN with SOC susceptibility factors are infected by some viral or microbial infection, they develop abnormal immune responses . It is rand TLR3 , HLA-A ad PTGER3 . Severald PTGER3 .HLA-C gene expression using the GWAS catalog database and found 74 SNPs. From these analyses, we determined top 10 SNPs with the highest p-values. We were further processed with the variant annotation tool SNPnexus to determine the annotation of prioritized SNP variations. After these analyses, two statistically significant SNPs were obtained and prioritized. In this case, we prioritized 2 SNPs at risk for SJS based on an analysis of the number of SNPs expanded using HaploReg version 4.1 and a p-value of < 10-8 to determine the functional annotation of the SNPs. The results of genetic variation are shown in Gene expression of SJS in human tissue was evaluated via the GTEx Portal database. This aims to determine the gene expression level in various tissues including in the skin tissue. We identified genomic variations from HLA-C gene in differential tissue expression in the human skin. By using the GTEx portal , we further emphasized that the variants of rs2074494 and rs5010528 encoded the HLA-C genes were a higher expression in the skin tissue to HLA-C expression–associated variants, we set out to determine the allele frequencies across transcontinental populations as shown in http://www.ensembl.org). Allele frequencies across populations differ for each HLA-C variant. Once we identified the candidate HLA-C gene expression.The allele frequency of the “rs2074494” T allele in the African population is expressed at a much lower level than that of the populations of America, Europe, and Southeast Asia. Taken together, the allele frequencies of the variants “rs2074494” and “rs5010528” indicated the contribution of differential variant prevalence for HLA-S gene which were reported to be potential associated in chickenpox disease [HLA-C gene, which has been linked to SJS and can lead to SCAR infection. Notably, the variants associated with HLA-C expression have not been reported for SJS. Basic research on the genetics of SJS and TEN to date has focused on HLA, the system associated with the presence of specific receptors, cytotoxic proteins, and the part of immunocytes during disease pathogenesis [HLA-C variants may be an essential quest that allows further understanding of global disease susceptibility.Another study revealed that  disease . In thisogenesis . ConsideHLA gene encodes several molecules that are crucial to the immune system. With that in mind, a strong relationship between HLA genes and autoimmune diseases has been demonstrated for more than half a century [HLA-B*15:02 in an Asian population. In contrast, the association with HLA-A*31:01 was only reported in Japan and Europe. and has a novel association between HLA-A*31:01 and CBZ-SJS/TEN in Indians [HLA genes can then be analyzed using publicly available databases. We used publicly available databases like the GTEx Portal, SNPnexus, and Ensembl. We identified genetic variants associated with HLA-C expression in skin tissue, the leading site of SCAR infection in SJS disease. It has previously been reported that specific HLA genotypes have been associated with the occurrence of severe skin disease due to drug-induced side effects (SCARs), which cases are included in SJS/TEN [The  century . Finding Indians . The ass SJS/TEN .The allele frequencies in all populations differ for each SNP, as shown in HLA-C gene across 16 human tissues. Even though HLA-C is highly expressed in whole blood, spleen, lung, and lymphocyte cells, the relevant disease variants (rs2074494 and rs5010528) are differentially expressed in the skin tissue. Overall, alleles for rs2074494 and rs5010528 have lower frequencies in Southeast Asia , Europe , and East Asia , as compared to the American population  and the African  population.In this study, we conducted a comprehensive bioinformatic analysis of SJS from genomic databases, revealing differential tissue expression of the


With rising incidence of skin cancer and relatively increased mortality rates, an improved diagnosis of such a potentially fatal disease is of vital importance. Although frequently curable, it nevertheless places a considerable burden upon healthcare systems. Among the various types of skin cancers, non-melanoma skin cancer is most prevalent. Despite such prevalence and its associated cost, scant proof concerning the diagnostic accuracy via Artificial Intelligence (AI) for non-melanoma skin cancer exists. This study meta-analyzes the diagnostic test accuracy of AI used to diagnose non-melanoma forms of skin cancer, and it identifies potential covariates that account for heterogeneity between extant studies.Scopus, PubMed, ScienceDirect, SpringerLink, and Dimensions) were examined to discern eligible studies beginning from March 2022. Those AI studies predictive of non-melanoma skin cancer were included. Summary estimates of sensitivity, specificity, and area under receiver operating characteristic curves were used to evaluate diagnostic accuracy. The revised Quality Assessment of Diagnostic Studies served to assess any risk of bias.Various electronic databases (A literature search produced 39 eligible articles for meta-analysis. The summary sensitivity, specificity, and area under receiver operating characteristic curve of AI for diagnosing non-melanoma skin cancer was 0.78, 0.98, & 0.97, respectively. Skin cancer typology, data sources, cross validation, ensemble models, types of techniques, pre-trained models, and image augmentation became significant covariates accounting for heterogeneity in terms of both sensitivity and/or specificity.Meta-analysis results revealed that AI is predictive of non-melanoma with an acceptable performance, but sensitivity may become improved. Further, ensemble models and pre-trained models are employable to improve true positive rating.The online version contains supplementary material available at 10.1186/s12911-023-02229-w. Skin cancer accounts for 32.5% of all diagnosed malignancies, and it has a prevalence of 7.96 million cases occurring globally each year among the general population . With rePathologically, skin cancer is categorized into either melanoma or non-melanoma. Albeit relatively rare, three hundred thousand annual cases of melanoma are determined as highly malignant, with a reported mortality rate of 1.6 per 100,000 worldwide , are lesCurrently, clinical examination and dermoscopic evaluation are major techniques for screening skin cancers . These sArtificial intelligence (AI) techniques are being employed to provide diagnostic assistance to dermatologists since most diagnoses rely principally on visual patterning recognition , a partiUntil present time, synthetic evidence regarding the performance of AI techniques applied for the diagnosis of non-melanoma skin cancer remains insufficient , 10. WitSummary of the performance of AI for diagnosing non-melanoma skin cancer with quantitative evidence so that AI’s utility assessment can be made with greater efficacy and objectivity.Identification of potential covariates as they relate to AI performance since it may improve through an adoption of those strategies indicated by these identified covariates whenever building AI models.Accumulation of knowledge of diagnostic test accuracy for AI in non-melanoma skin cancer takes place so that earlier and more accurate diagnosis of non-melanoma skin cancer is practical.In viewing the unfulfilled areas of knowledge, the purposes of this meta-analysis are therefore: 1) to meta-analyze the accuracy of diagnosis for non-melanoma skin cancer via machine learning and deep learning; and, 2) to examine potential covariates that can account for the heterogeneity found among these studies. The main contributions of this study are:The remainder of this paper is structured as follows. Related work section introduces prior reviews on the topic of diagnostic test accuracy, focusing on how these reviews were planned and evaluated. Material and methods section presents the research method adopted in this study. Results section describes the analytical findings based on collected data, Discussion section interprets and describes the significance of the findings, and Conclusions section summarizes the findings of the current study.Up until the most recent examples, a number of studies have started to review existing evidence related to AI techniques for skin-lesion classification , 35–37. This study was conducted according to the PRISMA statement   studies investigating the accuracy of non-melanoma skin cancer; 2) studies written in English; and, 3) studies adopting machine-learning or deep-learning techniques. Studies were dis-qualified for inclusion, if: 1) they only investigated the incidence of melanoma skin cancer; 2) studies were irrelevant to our research purpose; and, 3) full texts were unavailable for purposes of examination. We located 134 potentially eligible articles, of which 95 were excluded with reason . Only studies that adopted a neural network algorithm with more than one hidden layer were categorized as being part of the deep learning group, with others categorized as being part of the machine learning group for purposes of our study. For models based on deep learning, further recorded information including whether pre-trained models were utilized and whether image augmentation was implemented. Further, we extracted the original numbers of Regarding the quality of each of the included studies, we evaluated the risk of bias and applicability in accordance with the revised Quality Assessment of Diagnostic Studies (QUADAS-2) including four domains: sample selection, index test, reference standard, flow, and timing .Following the suggestion of prior evidence , sensitiDenseNet, ResNet, or AlexNet) were used (Yes or No), and whether image augmentation procedures were used by deep learning models (Yes or No) were undertaken to check for possible heterogeneity among studies. The significance level is set to 0.05 for present study.Several meta-regressions with plausible covariates, including types of non-melanoma skin cancer , whether data sources were publicly available (public or proprietary), whether cross-validation procedures were undertaken, whether ensemble models were adopted, types of AI technique employed (machine learning or deep learning), whether pre-trained deep learning models  and then intra-epithelial carcinoma 43.28%). About 76% of datasets were publicly available. Cross-validation procedures were adopted by near 22% of included studies, while approaches of ensemble models were employed by about 16%. Deep learning techniques (76%) were adopted more frequently than machine learning techniques (19%). Among 51 studies adopting deep learning, about 73% of these utilized pre-trained models for prediction, while nearly 65% of studies employed image augmentation techniques when building predictive models. Detailed characteristics of the inclusive studies is given in Tables % and the.28%. AboAccording to the QUADAS-2 tool , 18 out As shown in Table 2 tests to evaluate the heterogeneity of sensitivity and specificity. The test for equality of sensitivity and of specificity were both significant, χ2 (66) = 2702.33, p < 0.001 and χ2 (66) = 12,373.02, p < 0.001, indicating significant between-study heterogeneity existed for both sensitivities and specificities.Pooling sensitivity and specificity based on univariate meta-analysis of diagnostic test accuracy can sometimes be misleading . The bivp = 0.046). The corresponding specificity was close between basal cell carcinoma and intra-epithelial carcinoma , but a significant difference was still detected (p = 0.006).As shown in Table p = 0.686). Specificity was however significantly higher for studies which adopted public data sources  than proprietary data sources .Studies utilized public data sources, as displayed in Table p = 0.380). However, studies that implemented cross validation showed a significant lower specificity than studies that did not .As presented in Table p = 0.014), and a tied specificity .Studies that adopted ensemble models, as depicted in Table p = 0.001) but not sensitivity (p = 0.344).The studies that used deep-learning techniques, as showed in Table p = 0.048) rather than specificity (p = 0.263).As depicted in Table p = 0.413). There was however a statistically significant difference between studies adopted image-augmentation procedures and studies that did not .Table Considering the potential health threat posed by non-melanoma skin cancer and the advances of AI techniques made in recent years, it is timely to both synthesize and report the results in diagnosis of non-melanoma skin cancers based on AI. According to the included studies, our meta-analysis shows there to be diagnostic performance with a moderate sensitivity, a strong specificity and AUC. Sensitivity was significantly dependent on the types of non-melanoma skin cancer encountered and whether ensemble models were adopted, while specificity was significantly dependent on included covariates except for whether ensemble models were adopted and whether pre-trained models were used.Prior studies , 9 show In terms of differing types of non-melanoma skin cancer, the sensitivity of basal cell carcinoma was higher than those found in intra-epithelial carcinoma. Significant difference between basal cell carcinoma and intraepithelial carcinoma was observed. The potential reason that basal cell carcinoma reached a significant higher sensitivity may be due to more images of this type of skin cancer are included and thus more characteristics are learned than the other type of skin cancer . The specificity of basal cell carcinoma was lower than, but close to, that of intra-epithelial carcinoma. In words, there are few false positive results when using artificial intelligence to detect non-melanoma skin cancers.Data for building machine-learning models that are collected from public data sources, in general, are more frequently leveraged than proprietary data sources in the present study. It is therefore reasonable that predictive models based on public data sources often perform better than those based on proprietary data sources since data from public sources are better understood than data from proprietary sources. Our study confirmed studies that data used from public sources performs better in terms of both sensitivity and specificity than those of data used from proprietary sources. This finding was also reported by Dick et al. , but theIn order to prevent over-fitting , it is wEnsemble models are predictive models that combine predictions from more than one model into one model . They teThe summary sensitivity and specificity is  and  when deep-learning and machine-learning techniques were used, respectively; however, statistical significance difference was evident only in specificity. As illustrated in Table Pre-trained models are generalizable deep neural networks which are trained on large-scale data and can be transferred to many tasks . Simply In order to prevent over-fitting, deep learning usually required large amounts of data for purposes of training . WithoutFinally, our study meta-analyzed the diagnostic test accuracy based on PRISMA statement . Common Just like most meta-analyses, our study has its limitations. First, the interpretation of summary sensitivity and specificity should be approached cautiously since heterogeneity among studies exists. Further, 72 studies were excluded due to insufficient quantitative information. Future diagnostic studies aimed at predicting non-melanoma skin cancers are suggested to include sufficient quantitative information for subsequent meta-analysis to better characterize and profile these studies. The covariates identified in this study are purely based from a statistical viewpoint , future Our study aims to meta-analyze the diagnostic test accuracy of applying AI techniques to the diagnosis of non-melanoma type skin cancer which is already considered insufficient in review evidence. Without a better understanding of the performance of AI for the diagnosis of non-melanoma skin cancer, the potential of AI may not be fully realized. Furthermore, the results of this quantitative meta-analysis can provide a more objective synthesis of the AI performance for diagnosing non-melanoma skin cancer. Based on the findings of this study, the usefulness of AI can be assessed with greater facility and objectivity. Moreover, strategies for improving the performance of AI used for screening non-melanoma skin cancer are identifiable. A quick, safe, and non-invasive screening of non-melanoma skin cancers can thus be expected. By searching multiple online databases, 39 articles (67 studies) were included for purposes of meta-analysis. A bivariate meta-analysis of diagnostic test accuracy was undertaken to obtain summary sensitivity, specificity, and AUC. A moderate diagnostic performance of summary sensitivity, a strong summary specificity, and a strong AUC were all observed based according to a bivariate meta-analysis of diagnostic accuracy test. Types of non-melanoma skin cancer, whether data sources were publicly available, whether cross-validation procedures were undertaken, whether ensemble models were adopted, the types of AI technique employed, whether pre-trained deep-learning models were used, and whether image-augmentation procedures were all determined to partially explain some of the heterogeneity found among primary studies. Future studies may consider adopting the suggested techniques to have better predictive performance of AI for the effective diagnosis of non-melanoma skin cancer.Additional file 1.Additional file 2.