Iron deficiency is prevalent in women and patients with chronic kidney disease (CKD). Iron deficiency is not only related to anemia but contributes to adverse consequences for the kidney as well. Whether iron status is associated with renal outcomes after considering sex and anemia in patients with CKD stage 1–4 is unclear. Thus, we investigated the association of iron or iron saturation with renal outcomes in a CKD cohort. During a follow-up of 8.2 years, 781 (31.2%) patients met the composite renal outcome of renal replacement therapy and a 50% decline in renal function. In linear regression, iron was associated with sex, hemoglobin (Hb), and nutritional markers. In a fully adjusted Cox regression model, the male patients with normal iron had a significantly decreased risk of renal outcomes (hazard ratio (HR) 0.718; 95% confidence interval (CI) 0.579 to 0.889), but the female patients did not exhibit this association. The non-anemic patients (Hb ≥ 11 g/dL) had a decreased risk of renal outcomes , but the anemic patients did not. In the sensitivity analysis, transferrin saturation (TSAT) showed similar results. When comparing iron and TSAT, both indicators showed similar prognostic values. In conclusion, iron deficiency, indicated by either iron or iron saturation, was associated with poor renal outcomes in the male or non-anemic patients with CKD stage 1–4. Iron is a unique trace nutrient that participates in numerous fundamental biological reactions ,2,3. It Sex and anemia are two important confounders to be considered. Prior studies suggest that women have a higher prevalence of CKD while men progress at a faster rate of renal function decline ,20. The Anemia is prevalent in CKD patients. Patients with hemoglobin (Hb) <11 g/dL made up 32.2% of our cohort. Deficiency of erythropoietin and deficiency of iron are the two major reasons for anemia in CKD . Iron-deAccordingly, the purposes of our study were to explore the relationship between iron status and renal outcomes, as well as to investigate the impact of sex and anemia in this association among patients with CKD stage 1–4. Considering that the conventional iron biomarker transferrin saturation (TSAT) is susceptible to malnutrition and inflammation , we utilWe conducted a prospective, observational cohort study in two affiliated hospitals  of Kaohsiung Medical University in Southern Taiwan. There were 3659 CKD stage 1–5 patients enrolled in the Integrated CKD Care Program Kaohsiung for Delaying Dialysis from 11 November 2002 to 31 May 2009. CKD was staged according to the definition of the K/DOQI guidelines , and theTo study the impact of serum iron and sex on renal outcomes, we stratified these 2500 CKD subjects into 4 groups: “men with normal iron”, “men with low iron”, “women with normal iron”, and “women with low iron”, in accordance with the tertiles of the serum iron levels; that is to say, the patients in the first tertile of serum iron  were assigned to the low iron groups, while those in the second and the third tertiles of serum iron  were allocated to the normal iron groups. In the sensitivity analysis, to study the impact of TSAT and sex on renal outcomes, we divided the participants into another four groups: “men with normal TSAT”, “men with low TSAT”, “women with normal TSAT”, and “women with low TSAT”, according to the tertiles of TSAT; that is, subjects in the first tertile of TSAT  were taken as low TSAT, while those in the second and the third tertiles of TSAT  were seen as normal TSAT.In addition, to study the influence of serum iron and anemia on renal outcomes, the patients were grouped in line with the level of both serum iron and Hb. Individuals with Hb < 11 g/dL were classified as anemic , while Furthermore, we studied the correlation of the combined set of serum iron and TSAT with renal outcomes. In the same way, tertile 1 of the serum iron levels was used to partition the subjects into low iron and normal iron groups, while tertile 1 of the TSAT levels was utilized to group the patients into low TSAT and normal TSAT groups.Baseline parameters were acquired from medical records and visits with patients at enrollment. It included demographic features (age and sex); medical histories (diabetes mellitus (DM), cardiovascular disease (CVD), hypertension (HTN), hyperuricemia, metabolic syndrome (MtS), and malnutrition–inflammation); clinical parameters , body mass index (BMI), and malnutrition–inflammation score (MIS)); and laboratory data , C-reactive protein (CRP), bicarbonate, phosphorus, calcium, uric acid, glycosylated hemoglobin (HbA1c), and urine protein to creatinine ratio (UPCR)).The medical histories were collected by chart review by two to three nephrologists; DM and HTN were defined by clinical diagnosis. CVD was defined as a clinical diagnosis of ischemic heart disease, congestive heart failure, and cerebrovascular disease. Hyperuricemia was defined as uric acid > 7.2 mg/dL in men, >6.5 mg/dL in women, or that under urate-lowering therapy. MtS was defined by the meeting of at least 3 of the following 5 criteria proposed by the Health Promotion Administration, Ministry of Health and Welfare of Taiwan: (1) fasting blood glucose ≥ 100 mg/dL or previously diagnosed DM; (2) systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥85 mmHg or a previous diagnosis of HTN; (3) high-density lipoprotein cholesterol < 40 mg/dL in men or <50 mg/dL in women; (4) triglyceride ≥ 150 mg/dL; and (5) waist circumference ≥ 90 cm in men or ≥80 cm in women .The MIS, first proposed by Professor Kalantar-Zadeh for dialysis patients  and modiFerritin was measured in serum using a two-site immuno-enzymatic assay with the Beckman Coulter UniCel-DxI 800 . Iron was measured in serum using an Fe reagent via a timed endpoint method with the Beckman Coulter UniCel-DxC 800 . Transferrin was measured in serum using a transferrin reagent via the turbidimetric method with the Beckman Coulter UniCel-DxC 800 . Additionally, TIBC values were obtained by multiplying the transferrin (mg/dL) by a coefficient of 1.4. High-sensitivity CRP was measured in serum using the near-infrared particle immunoassay rate method with the Beckman Coulter UniCel-DxC 800 . The laboratory data were averaged and analyzed three months before and after enrollment in the CKD care system.There were 2 main outcomes assessed: (1) renal replacement therapy (RRT) and (2) the composite endpoint of RRT and a 50% decline in eGFR. RRT was defined as the entry into long-term dialysis therapy  or the receiving of kidney transplantation. For the outcome of RRT, the subjects were censored due to death or loss of follow-up.The statistical results of the baseline characteristics of the patients were expressed as mean ± standard deviation (SD) for the continuous variables with normal distribution, as median  for the continuous variables with skewed distribution, and as percentages for the categorical data.p-value of <0.05.The significance of the differences for the normally distributed continuous variables among the groups was tested using one-way ANOVA analysis, while the difference for the non-normally distributed continuous variables was tested using a Kruskal–Wallis analysis. Additionally, the difference in the distribution of categorical variables among groups was tested using the chi-square test. Cox proportional hazard regression models were performed, in separate groups of males and females, to assess the association of serum iron with the outcomes, the relationship of TSAT with the outcomes, and the correlation of the combined set of serum iron and TSAT with the outcomes. The adjusted hierarchical covariates were as follows: model 1 adjusts for age, eGFR, and log-transformed UPCR; model 2 adjusts for the covariates in model 1 plus DM, CVD, severe liver disease, cancer, mean blood pressure (BP), and BMI; and model 3 adjusts for the covariates in model 2 plus albumin, log-transformed CRP, Hb, log-transformed ferritin, phosphorus, total cholesterol, and HbA1c. Statistical analyses were conducted using SPSS 21.0 for Windows , with statistical significance set at a two-sided In total, 2500 CKD stage 1–4 patients (1601 men and 899 women) were included and analyzed in this study. The baseline demographics, medical histories, clinical parameters, and laboratory indices are detailed in 2 (interquartile range (IQR): 26.7–49.7 mL/min/1.73 m2) and 12.8 ± 2.2 g/dL, respectively. During the follow-up of 8.2 years, there were 313 (19.6%) male patients starting RRT; 432 (27.0%) met the composite endpoint of RRT combined with a 50% decline in eGFR, and 274 (17.1%) expired before RRT. In contrast to the male subjects with normal iron, those with low iron tended to have DM, CVD (particularly congestive heart failure and cerebrovascular disease), malnutrition–inflammation, higher MIS, lower eGFR, higher UPCR, lower Hb, decreased albumin, elevated WBC, elevated CRP, lower bicarbonate, and higher HbA1c. Likewise, the male patients in the low iron group were likely to have poor renal outcomes and higher mortality before RRT compared to those in the normal iron group.Among the male participants, the mean age (±SD) was 62.8 ±14.4 years; 764 (47.7%) had DM; 365 (22.8%) had a history of CVD; 957 (59.8%) had HTN; and 370 (23.1%) suffered from malnutrition–inflammation. The overall levels of eGFR and Hb were 38.2 mL/min/1.73 mIn the female participants, those with low iron tended toward DM and malnutrition–inflammation, followed by higher MIS, higher UPCR, lower Hb, lower albumin, elevated WBC, elevated CRP, and elevated HbA1c in comparison with those with normal iron. Moreover, the female patients in the low iron group were inclined to receive RRT and had higher mortality before RRT in contrast to those in the normal iron group.In summary, both the male and the female CKD stage 1–4 patients with low iron levels were likely to suffer from DM and malnutrition–inflammation. In addition, worse baseline renal function (lower eGFR or higher UPCR), more severe anemia, declines in nutritional status , inflammation (including elevated WBC and CRP levels), poor renal outcomes, and higher mortality before RRT were disclosed in the low iron subjects of both sexes. Notably, higher values of WBC, CRP, and MIS were present in the low iron group of men in comparison to the low iron group of women. With regard to Hb levels, the women’s Hb levels were lower overall than the men’s, regardless of the iron status in both sexes.The iron status of the study participants is depicted in Furthermore, For the male patients, one SD increase in serum iron was associated with a 16.2% decrease in RRT (hazard ratio (HR) 0.838; 95% confidence interval (CI) 0.717 to 0.980), along with an 11.8% decrease in RRT and a 50% decline in eGFR . On the other hand, for the female patients, there were no significant relationships between serum iron and adverse renal outcomes in the fully adjusted model.As for the pre-specified groups of low iron and normal iron, in comparison to the male subjects with low iron, those with normal iron had a significantly reduced risk of RRT of 36.0% , accompanied by a 28.2% reduction in the risk of the composite endpoint of RRT combined with a 50% decline in eGFR  in the fully adjusted model. By contrast, the female patients with normal iron did not present a significantly decreased risk of adverse renal outcomes compared to those with low iron in the fully adjusted model.Similarly, the negative association between TSAT and adverse renal outcomes was only exhibited in the males, regardless of whether TSAT was analyzed as a continuous variable or a category variable . For theAs per the results demonstrated in Regarding the groups of low iron and normal iron, the non-anemic patients with normal iron had significantly decreased risks of RRT and the composite endpoint of RRT combined with a 50% decline in eGFR, with HRs (95% CI) of 0.699 (0.525 to 0.929) and 0.715 (0.568 to 0.898), respectively, compared to those with low iron in the fully adjusted model. Conversely, the anemic patients with normal iron did not present a significantly decreased risk of adverse renal outcomes in comparison to those with low iron in the fully adjusted model.Likewise, the negative association between TSAT and adverse renal outcomes was only exhibited in the non-anemic subjects . For theWe further separately divided the male subjects into four groups according to serum iron and TSAT levels, as p-value) of −0.238 , −0.282 , and −0.005 , respectively. In contrast, the patients with higher Hb, albumin, and phosphorus were prone to having a higher serum iron, with β coefficients  of 0.123 , 0.150 , and 0.075 , respectively.We further conducted multivariate linear regression to analyze the correlation factors of serum iron. As p < 0.001), but for the women, the MIS did not have a significant statistical correlation with serum iron .Moreover, this table also displays different degrees of negative correlation between the MIS and serum iron in both sexes. For the men, a higher MIS was significantly associated with lower serum iron  in the males and non-anemic patients with CKD stage 1–4. Therefore, both serum iron and TSAT were important predictors. In our cohort, the male patients in the first tertile of iron (<67 μg/dL) or in the first tertile of TSAT (<24.6%) were associated with a higher risk of poor renal outcomes, while the male patients with both iron ≥ 67 μg/dL and TSAT ≥ 24.6% had a lower risk for poor renal outcomes.Iron deficiency, which affects up to 25% of the general population, is one of the most common nutritional disorders worldwide ,33, occuThere are two forms of iron deficiency. Apart from absolute iron deficiency, reflecting the paucity of iron stores in the bone marrow, a certain percentage of CKD patients suffer from functional iron deficiency representing reduced iron bioavailability despite adequate body iron storage ,37,38. Tp = 0.041). This sex difference could be explained as being the result of different body compositions and by the divergent impacts of inflammation among the sexes. With regard to body composition, physiologically men have a significantly higher skeletal muscle mass distribution than women [The relationship between serum iron and poor renal outcomes, especially for the male CKD patients, was postulated to be due to the more detrimental influence of muscle wasting, malnutrition, and inflammation in men, causing increased hepcidin production and decreased iron released to the blood, inducing decreased energy metabolism for high-energy-demand organs such as kidneys. Indeed, for the multivariate linear regression we performed , a negatan women ,41 in boan women  and CKD an women ,44. Thisan women ,46,47,48an women . As muscan women ,51, malean women ,52. In aan women . The imman women  and a sean women  might bean women . As ironan women , it mighan women ,17.Our finding of the relationship between iron and renal outcomes in non-anemic CKD patients might highlight the momentousness of iron in bioenergetics beyond heme synthesis. Conversely, a lack of significance was found in the correlation between serum iron and renal outcomes among anemic CKD subjects, as revealed in Furthermore, we found that both serum iron and TSAT were relevant to renal outcomes. Traditionally, TSAT and ferritin are the most frequently used biomarkers to assess iron stores and provide guidance for iron treatment to clinicians ,35,36. NSeveral limitations of this study need to be mentioned. First, the observational inherence of our study could not allow us to establish a causal relationship between serum iron and the outcomes. Further well-designed interventional studies are required to confirm the association between iron levels and the renal outcomes in CKD populations. Second, the basic research to validate the mechanisms of renal function deterioration induced by iron deficiency was lacking. Third, the data on iron indices were obtained at a single time point, which is an impediment to discerning the effect of changes in iron markers on clinical outcomes over time. Fourth, the absence of the measurement of hepcidin and erythropoietin precludes the ability to interpret the state of iron availability and the capacity of hematopoiesis, respectively. Fifth, we did not examine the levels of sex hormones, which could strengthen the postulations of sex disparities in the relationship between serum iron and renal outcomes in this study. Sixth, our study included patients from an earlier cohort.In conclusion, our study suggests that serum iron and TSAT are negatively correlated with poor renal outcomes (RRT or RRT + 50% decline in eGFR) in males and non-anemic patients with CKD stage 1–4. Both serum iron and TSAT were important predictors. This finding provides the potential implications for iron therapy and the augmentation of the screening of iron biomarkers in early-stage CKD as treatable risk factors of renal function deterioration. Further research is needed to validate our findings in terms of the impact of iron replacement treatment on renal outcomes.


The COVID-19 pandemic brings great pressure to the public health systems. This meta-analysis aimed to compare the clinical outcomes among different virus variants, to clarify their impact on medical resources and to provide evidence for the formulation of epidemic prevention policies.A systematic literature search was performed in the PubMed, Embase, and Cochrane Library databases using the key words “Omicron” and “Delta.” The adjusted Risk ratios (RRs), Odds ratios (ORs) and Hazard ratios (HRs) were extracted, and RRs and Rate difference % (RD%) were used to interpret the risk estimates of the outcomes ultimately.hospitalization = 0.45, 95%CI: 0.40–0.52; RRdeath = 0.37, 95%CI: 0.30–0.45; RRICU = 0.35, 95%CI: 0.29–0.42; RRmechanical ventilation = 0.33, 95%CI: 0.25–0.44). The change of both absolute and relative risks for hospitalization was more evident  and a significant increase was observed for the absolute differences in death in the elderly ; the change of the absolute differences in the risk of hospitalization and death were most markedly observed in the patients with booster vaccination .Forty-three studies were included, with 3,812,681 and 14,926,841 individuals infected with SARS-CoV-2 Delta and Omicron variant, respectively. The relative risks of hospitalization, death, ICU admission, and mechanical ventilation use after infection with the Omicron variant were all significantly reduced compared those after infection with the Delta variant (RRThe ability of the Omicron variant to cause severe clinical events has decreased significantly, as compared with the Delta variant, but vulnerable populations still need to be vigilant. There was no interaction between the vaccination doses and different variants. A signiBased on the enormous pressure brought by the COVID-19 epidemic to the global public health system, understanding the difference in the clinical outcomes between the current epidemic variant Omicron and Delta is important to formulate more accurate epidemic prevention policies. The multi-level meta-data covering multiple regions worldwide remains limited. Concurrently, the estimation of the absolute risk change is of more significance to public health. Therefore, using data from cohort and registration studies comparing Delta and Omicron variants worldwide, we conducted a meta-analysis to investigate the difference in hospitalization rate and risk of severe clinical events between the Omicron and Delta variants to contribute to the establishment of further public health policies.2.This analysis was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines  and regi2.1.A comprehensive search was conducted on PubMed, Embase, and the Cochrane Library for all relevant articles published from the emergence of COVID-19 on December 24, 2021, to the December 31, 2022. The search terms used were “Omicron” and “Delta.” The reference lists of identified studies and reviews were hand searched for potentially relevant studies not previously identified in the database search.2.2.The duplicates were removed. Then, the studies were screened by title and abstract, later followed by full text reviewed by six investigators. In case of disagreement, a consensus was reached by discussion. Studies were included if they fulfilled the following criteria: (1) cohort or registry study; (2) used pre-matched or post-hoc multivariate adjustment; (3) provided at least one of the following clinical outcomes of Omicron and Delta patients: hospitalization, ICU admission, mechanical ventilation use, and death; and (4) the sample size of the study was >100. The exclusion criteria were (1) systematic review, case report/series, editorial, letter, abstract, and animal study; and (2) with overlapping population.2.3.Data, including name of first author, published time, study region, study design, sample size, age, match or multivariate analysis method and variables, and outcome indicator, were extracted using a standardized data collection form. Two researchers independently assessed the study quality using the Newcastle-Ottawa Scale NOS;  based on2.4.2 statistics. If the heterogeneity among studies was >50%, the random-effect model was used. Otherwise, a fix-effect model was chosen. Based on the included articles, we performed subgroup meta-analyses according to the age , vaccination status , patient source . The Begg’s test was used to evaluate potential publication bias (significant when p < 0.05). Sensitivity analyses were performed to evaluate the robustness of the results by omitting studies one by one.Stata 12.0 software  was used to perform the meta-analysis. The adjusted RRs, ORs, and HRs were used to pool the risk estimates of outcomes when available. When the effects with 95% confidence interval (CIs) were not shown directly in a publication, they were calculated by using a two-by-two frequency table. RRs (Omicron vs. Delta) were used to interpret the risk estimates of outcomes ultimately. The weighted natural logarithm of the RRs with their 95% CIs was used to obtain the pooled relative risk estimates. Statistical heterogeneity was assessed using the I3.3.1.Of the 5,720 articles identified, 273 were eligible for full-text screening; 36 cohort and 7 registry studies  were inc3.2.I2 = 98.5%; p < 0.001); hence, effect size was calculated via the random-effects model. The summary RR was 0.45, indicating a statistically significant decreased risk of hospitalization with Omicron variant compared to Delta variant  and Twenty-three studies  were included in the analysis for clinical outcome of ICU admission and mechanical ventilation. Compared with the Delta variant, the Omicron variant was associated with a reduced risk for ICU admission , the Education Department of Jilin Province (JJKH20211153KJ).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Irinotecan (SN-38) is a potent and broad-spectrum anticancer drug that targets DNA topoisomerase I (Top1). It exerts its cytotoxic effects by binding to the Top1-DNA complex and preventing the re-ligation of the DNA strand, leading to the formation of lethal DNA breaks. Following the initial response to irinotecan, secondary resistance is acquired relatively rapidly, compromising its efficacy. There are several mechanisms contributing to the resistance, which affect the irinotecan metabolism or the target protein. In addition, we have demonstrated a major resistance mechanism associated with the elimination of hundreds of thousands of Top1 binding sites on DNA that can arise from the repair of prior Top1-dependent DNA cleavages. Here, we outline the major mechanisms of irinotecan resistance and highlight recent advancements in the field. We discuss the impact of resistance mechanisms on clinical outcomes and the potential strategies to overcome resistance to irinotecan. The elucidation of the underlying mechanisms of irinotecan resistance can provide valuable insights for the development of effective therapeutic strategies. Camptotheca acuminata [Irinotecan CPT-11) is a chemotherapeutic agent that causes cancer cell killing by poisoning topoisomerase I (Top1) in the cell. It is a semisynthetic analog of camptothecin, which was originally isolated from the Chinese/Tibetan ornamental tree 1 is a chcuminata ,3. Resiscuminata ,5,6. Bescuminata ,8,9 or dcuminata ,11. It icuminata , changescuminata ,14,15, ocuminata ,17,18,19Importantly, both in experimental and clinical settings, secondary resistance usually develops gradually in the course of multiple exposures to the drug. It is unclear why changes in transcriptome ,19,20,21One of the classes of drugs that are frequently used in cancer therapy is inhibitors of DNA supercoil relaxing topoisomerases, including Top1 and Top2. Type I topoisomerases (Top1) cause relaxation of super helical DNA by generating a transient single-strand nick, followed by DNA relaxation and re-ligation. The enzyme subtypes perform very specialized functions, e.g., Class IA can only relax negative supercoiled DNA, whereas Class IB can introduce positive supercoils, relaxing and separating DNA molecules in daughter chromosomes after DNA replication. Top1 plays major role in transcription and replication and is highly active in pericentromeric and centromeric regions of the genome ,37,38,39Major Top1 or Top2 inhibitors function by stabilizing the transient complexes formed between these enzymes and DNA ,42. StabA most widely used Top1 inhibitor, irinotecan is a prodrug that, upon activation, generates an active compound, SN-38 ,46,47,48High-intensity transcription and replication enhances the supercoiling of DNA to levels that can impede or halt these processes. As a potent transcription amplifier and replication accelerator, the proto-oncogene MYC must manage this interfering torsional change. In a recent study, a direct association of MYC with Top1 and Top2 was demonstrated . Beyond In the USA, irinotecan has been approved for use against colorectal cancer in combination with 5-fluorouracil (5-FU) and leucovorin (FOLFIRI regimen). With therapy regimens like FOLFIRI, the median survival rate of a patient with metastatic colorectal cancer has improved from 8 months to 24 months . IrinoteAnother promising combination of irinotecan is with antibodies against EGFR, such as Cetuximab, for treatment of patients with wild-type K-Ras colorectal cancers and certain other cancer types, with 5-FU/leucovorin as a first-line treatment . It is iBeside irinotecan, there are several camptothecin derivatives poised to become pharmacological agents in various cancer treatment protocols. Among them, exatecan shows a great promise; it is 6 times more active than SN-38 and 28 times more active than topotecan ,66. In aDxd and other developed conjugates of irinotecan derivatives with antibodies (TOP1-ADC) provide a series of advantages. Monoclonal antibody-mediated active targeting offers both selectivity and extremely high affinity because of specific antibody–antigen binding, which can distinguish tumor versus healthy cells based on antigen expression levels ,78. ConsUpon administration through intravenous injection, a fraction of irinotecan is converted in the blood to active form SN-38 by carboxylesterases, which could lead to circulatory or digestive complications . NeverthUGT1 and clinical outcomes, and have strongly supported the role of the UGT1A enzyme pathway in mediating the response to SN-38 [UGT1A1*28, which is associated with reduced UGT1A1 activity and irinotecan-induced severe neutropenia [UGT1A1*28 testing of potential irinotecan users [High sensitivity to irinotecan associates with genetic variance in the UGT1A, CYP3A, and ABC gene families which play a major role in the metabolism of the drug ,49,88. Sto SN-38 ,90. The tropenia ,90  transporters, such as the multi-drug resistance 1 P-glycoprotein gene (ABCB1) and the multi-drug resistance-associated protein 2 gene (ABCC2) , which fThe xenobiotic receptors PXR/SXR and the retinoic receptor RXR that regulate expression of UGT1A1, CYP3A4 and ABC transporters significantly contribute to irinotecan resistance ,103,104.An important factor in resistance to irinotecan-containing therapies is cancer cell stemness. Cancer stem cells (CSC) have self-renewing capabilities due to the expression of a series of transcription factors, such as NANOG, OCT4, or SOX2. Generally, CSC demonstrate drug resistance due to a number of properties, including low rate of division, thus spending the majority of time in G0 , high leIndeed, expression of CD133, a marker for stemness of CRC, was found to correlate with the resistance. Such CD133+ tumorigenic cells in colon cancer represent approximately 2.5% of the total tumor cells . These cDNA breaks following irinotecan treatment can activate apoptosis via p53 and other mechanisms ,53,115. Expression of the irinotecan target Top1 was reported to be a predictive biomarker for irinotecan sensitivity ,126. FurTop1 has four domains: the NH2-terminal domain (residues 1–214), the core domain (residues 215–635), which can be divided into subdomains I, II, and III, the linker domain (residues 636–712), and the COOH-terminal domain (residues 713–765). The poorly conserved linker domain, which connects the core and COOH-terminal domains, is highly flexible  and is dA number of point mutations in Top1 that confer resistance to SN38 have been identified in tumor cell culture  . HoweverIn a recent development, we studied a puzzling need of multiple exposures to drugs in selection of resistant cancer cell mutants in culture. Our investigation involved a cloned, genetically identical population of HCT116 colon cancer cells. This model could recapitulate clinical conditions in clonal emergence and evolution of cancers. Multiple exposures of the genetically identical population to irinotecan in a dose escalation setting led to the evolution of drug resistance. Our initial expectation was that conventional resistance mechanisms would emerge, such as Top1 mutations or alterations in the transcriptome landscape that could promote cell survival. To elucidate these mechanisms, we independently selected three clones and conducted whole genome sequencing and transcriptome analysis, comparing them to the parental irinotecan-sensitive clone. Surprisingly, RNAseq did not demonstrate any changes in gene transcription related to drug metabolism, detoxification mechanisms, or MDR pumps, indicating that alterations in the transcriptome were unlikely to be involved in the development of resistance.Importantly, we detected hundreds of thousands of SNPs and InDels in the resistant mutants compared to the parental clone. Among them, we did not find mutations that affect Top1 or genes that belong to pathways associated with either cell survival or DNA repair. Therefore, it is unlikely that changes in gene function or expression are involved in this adaptation process .Strikingly, 15% of the mutations in the three independent isolates were identical. This large number of common mutations clearly indicates a non-random mechanism for their generation. Metadata analysis indicates that the mutations occurred at Top1 binding/cleavage sites in the genome. Interestingly, the majority of these sites corresponded to various types of satellites, including alpha satellites and satellite-II, indicating that Top1 preferentially interacts with and cleaves DNA at satellite sites. In the parental clone of the HCT116 cells, we observed a significantly higher number of these sites than in the reference genome that represents an average of several normal human genomes. Considering that the HCT116 line demonstrates satellite instability, it appears that this instability generates additional Top1 binding/cleavage sites in the process of cancer evolution. This increased number of Top1 sites may significantly contribute to the elevated sensitivity of these cells to irinotecan.Importantly, mutations generated in the irinotecan resistance mutants carried signatures of the double strand breaks repair mechanisms (HR: Homologous recombination and NHEJ: Non-homologous end joining). Accordingly, considering their locations at the Top1-binding sites, these mutations must result from the repair of DSB created by Top1 upon SN-38 treatments.The most striking finding was that in the case of heterozygocity in the parental clone: where one allele was normal (found in the reference genome) and another one mutated due to cancer evolution, the latter allele was lost preferentially upon development of irinotecan resistance. Such loss of heterozygocity can only result from the HR repair of DSB. The disproportionately high loss of the “cancer allele” indicated that Top1-generated DSB took place in this allele preferentially, and it was repaired by copying of the reference genome sequence from the homologous chromosome. Therefore, reversion to the normal reference genome allele upon treatment with SN-38 must eliminate the Top1 cleavage/binding site at this place. Accordingly, we hypothesized that upon initial treatments with SN-38, Top1 that associates with specific binding sites on the chromosomes creates single strand breaks that can be converted to toxic DSB at these sites. Repair of these DSBs via HR (and possibly NHEJ) creates mutations at these sites that prevent binding of Top1 to them upon following exposures to the drug. Indeed, in the resistant mutants, we observed a significantly reduced association of Top1 with the genome. Furthermore, upon exposures of the resistant mutants to SN-38, we observed dramatically fewer DSB, as monitored by formation of the γH2AX foci .Taken together, these findings suggest that the primary pathway for adaptation to SN-38 is not linked to functional gene mutations, such as Top-1, or alterations in gene expression. Rather, mutations are generated after each exposure to the drug, which effectively “close” Top1 binding/cleavage sites on the chromosomes. These mutations gradually accumulate upon multiple exposures and ultimately render cells resistant to the drug. In other words, the development of irinotecan resistance is an inherent feature of the drug’s mechanism of action, where resistant mutations are directly produced from the repair of DSBs caused by Top1. Due to this intrinsic mechanism, resistance can be acquired rapidly, within just a few cycles of drug administration.These findings suggest interesting strategies for the suppression of the development of irinotecan resistance. Indeed, the uncovered mechanism of the resistance development is dependent on the efficiency of the DSB repair. According to this analysis, HR repair is the major factor in generating resistance mutations, but NHEJ may also be actively involved in their generation. Therefore, the model predicts that inhibiting HR alone or in combination with NHEJ would not only increase the sensitivity of cancer cells to irinotecan, but also prevent the development of secondary resistance.Another interesting conclusion from this mechanism is that, since the number of Top1 sites is gradually reduced upon development of the resistance, Top1’s ability to relax DNA supercoils should gradually get reduced. Since relaxation of DNA supercoils is essential for replication and transcription, the DNA relaxation activity of Top1 must be taken over by another enzyme, most likely Top2. Accordingly, development of resistance to irinotecan may enhance sensitivity of cells to Top2 inhibitors, such as doxorubicin. This possibility may guide the patient treatment strategy.


Spodoptera eridania and the damage it has caused to crop systems in recent years has raised concerns about its potential risks. In this study, we aimed to map the invasion risk of S. eridania worldwide based on an optimized MaxEnt model. The results indicated the suitable habitat concentrated in southern North America, South America, western Europe, central Africa, southern Asia, and eastern Oceania. Under climate change, suitable habitats for S. eridania will expand and shift to higher latitudes in the future. Countries without S. eridania invasion but that are at invasive risk, such as the European Union, Southeast Asian countries, and Australia should take appropriate quarantine measures to prevent the entry of this pest.The invasion of Spodoptera eridania), a polyphagous crop pest native to tropical America, has been found in Africa (2016) and India (2019), causing defoliation and damage to the reproductive structures of cassava, soybean, and tomato. The damage caused by this pest to crop systems has raised concerns regarding its potential risks. Therefore, we predicted the potential geographical distribution of S. eridania under climate change conditions using 19 bioclimatic variables based on an optimized MaxEnt model. The results showed that annual precipitation (bio12), mean temperature of the warmest quarter (bio10), and precipitation of the driest month (bio14) were important bioclimatic variables influencing the potential distribution. The prediction showed that the suitable habitat area was approximately 3426.43 × 104 km2, mainly concentrated in southern North America, South America, western Europe, central Africa, southern Asia, and eastern Oceania. In response to global climate change, suitable habitats for S. eridania will expand and shift to higher latitudes in the future, especially under the SSP5-8.5 scenario. Because of the current devastating effects on crop production, countries without S. eridania invasion, such as the European Union, Southeast Asian countries, and Australia, need to strengthen phytosanitary measures at border ports to prevent the introduction of this pest.The southern armyworm ( Spodoptera species appear to be significant invasive pests globally. This genus consists of more than 30 species, approximately half of which are economically important pests such as Spodoptera frugiperda , S. exigua (the beet armyworm), and S. exempta (the African armyworm) [Spodoptera eridania  (Lepidoptera: Noctuidae) , another significant invasive crop pest of Spodoptera, has expanded its range across multiple continents resulting in defoliation and damage to the reproductive structures of plants [Invasive crop pests have posed a threat to global agricultural production and food security, as they can reduce the yield and the value of crops and cause economic losses . Recent rmyworm) . These prmyworm) ,5. Theirrmyworm) ,7. SpodoStoll, 171  are predictive tools that express the effects of environmental change on species distribution . MaxEnt In this study, we used an optimized MaxEnt model to map the invasion risk of the SAW worldwide under near-current and future climate scenarios as follows: (1) the significant bioclimatic variables affecting the potential geographical distribution; (2) potential geographical distribution under the near-current climate; (3) the climate change impact on potential geographical distribution; and (4) the spatial variation of potential geographical distribution. This study aims to serve as a valuable reference for preventing SAW invasion worldwide.https://www.gbif.org/, accessed on 23 November 2022), the Center for Agriculture and Bioscience International , Bold Systems , and the published literature [Global occurrence data (including coordinates) and distribution region information of the SAW were obtained from the Global Biodiversity Information Facility , including 19 bioclimatic variables (Climate data were downloaded from the World Climate Database (ariables  with a sariables  and corrariables .MaxEnt (version 3.4.1) was used to predict the potential geographical distribution of SAW under current and future climate scenarios. The complexity of the MaxEnt model is closely related to that of the regularization multiplier (RM) and feature combination (FC) parameters. The ENMeval package was used to evaluate the complexity of the model by testing the Akaike information criterion correction (AICc) value corrected by the MaxEnt model under different RM and FC parameter combinations . In thisThe model’s performance was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC). The value of the AUC ranged from 0 to 1; the higher the value, the better the model performance .The prediction results from MaxEnt were imported into ArcGIS and converted into raster files. The suitability of the SAW ranged from 0 to 1. According to the maximum test sensitivity plus specificity logistic threshold (0.1254), the reclassify tool of ArcGIS was used to divide the suitability into four fitness classes: “unsuitable”, “low”, “moderate”, and “high”.The “Calculate Geometry” tool in the attribute table of ArcGIS was used to calculate the area for the suitable habitat in the projected coordinate system and the latitude and longitude of the centroid of the potential geographical distribution in the geographic coordinate system under different climate scenarios.The analysis of spatial variation in the potential geographic distribution was achieved in ArcGIS and was shown as “unchanged”, “expansion”, and “contraction”.The model optimization results showed that when RM = 2 and FC = LQH, the corresponding AICc value was the lowest (AICc = 0) . FurtherJackknife results showed that the important bioclimatic variables affecting the potential geographical distribution of the SAW were the mean temperature of warmest quarter (bio10), annual precipitation (bio12), and precipitation of driest month (bio14) . The env4 km2 and were mainly located in central and northern South America, central Africa, southern Asia, southeastern North America, eastern Oceania, and western Europe. The corresponding suitable habitat areas on each continent and their proportion of the total risk area were 1213.39 × 104 km2 (35.41%), 703.87 × 104 km2 (20.54%), 651.43 × 104 km2 (19.01%), 456.04 × 104 km2 (13.31%), 252.24 × 104 km2 (7.36%), and 149.46 × 104 km2 (4.36%)  .The high suitability habitats for the SAW were mainly located in the south-eastern USA, eastern Mexico, Cuba, and Puerto Rico (North American regions); central Bolivia, southwestern and eastern Brazil, southeastern Paraguay, northeastern Argentina, and northwestern Uruguay (South American regions), eastern Madagascar (Africa), central Vietnam, the Philippines, southern Pakistan (Asia), and southwestern Papua New Guinea (Oceania) .The potential geographical distribution of the SAW under future climate scenarios is shown in From a suitability perspective, the high-suitability habitat area increased in the 2050s, mainly in China, the USA, and Brazil, and remained largely unchanged in the 2030s. The moderate-suitability habitat area increased under the four conditions, with the overall increase being similar, mainly located in Europe (France), Asia (India), and Oceania . The low-suitability habitat area was increased under the scenario SSP5-8.5 in the 2030s and SSP1-2.6 in the 2050s, mainly located in South America (Brazil) and Asia (China), and was decreased under SSP1-2.6 in the 2030s and SSP5-8.5 in the 2050s, mainly located in Africa (Chad and South Sudan) .Analysis of spatial changes in potential geographical distribution allows for a more intuitive representation of the effects of climate change on the potential habitats of species. In this work, the spatial variation in the potential geographical distribution of the SAW under different future climates was expressed as “unchanged”, “expansion”, and “contraction”, compared to that under near-current conditions .4 km2.Under future climate conditions, the expansion of suitable habitats was mainly located in North America , South America (Brazil and Argentina), Europe , Africa , Asia , and Oceania . The greatest expansion of suitable habitat occurred in the 2050s under the SSP5-8.5 scenario, and the expansion area was 464.40 × 104 km2) occurred under the SSP5-8.5 climate scenario in the 2050s, mainly in northern South America, central Africa, and Asia (India and Thailand).The contraction area indicates that under future climatic conditions, this habitat will no longer be suitable for the SAW, and the habitat will be lost. For the SAW, the largest area of habitat loss (397.94 × 104 km2, 397.94 × 104 km2, and 3028.49 × 104 km2, respectively.In summary, under the SSP5-8.5 scenario in the 2050s, the spatial variation in potential geographical distribution for the SAW was the greatest, with the “expansion”, “contraction”, and “unchanged” areas being 464.40 × 10The centroid of the potential geographical distribution was analyzed to assess the migration of this species’ suitable habitats in latitudinal and longitudinal coordinates under the influence of climate change. In this study, the potential geographical distribution centroids of the SAW in each continent under different climate scenarios were calculated  and are In summary, compared with that in the near-current climate, the centroid of suitable habitats under future climate scenarios for the SAW shifted to higher latitudes, indicating that the potential geographical distribution of the SAW would occupy a wider latitudinal range under the impact of climate change.The SAW threatens the agroecosystem due to its polyphagous nature and environmental adaptability. In this study, we explored the impact of changes in temperature and precipitation on the potential geographical distribution of this invasive species using the MaxEnt model.In recent years, the CLIMEX and MaxEnt models have been widely used to explore the relationship between distribution patterns and climate . Both moTemperature plays an important role in the development of insects and can directly influence their life cycle, especially extreme temperatures, and determine their potential geographical range ,20. Our Precipitation can, directly and indirectly, influence the spread and population establishment of invasive crop pests ,20. For The results of this study suggest that SAWs have a wide range of suitable habitats in areas outside their origin. Regarding the impact of climate change on potential suitable habitats, SAWs had the largest suitable habitat under SSP5-8.5 in the 2030s, suggesting that this environmental condition is more suitable for the spread and development of this species’ population than other climatic conditions are. In future climate conditions, the SAW-suitable habitats will expand towards high latitudes; however, certain habitats in Africa will be lost, which is consistent with previous studies . This maGlobal climate change, particularly global warming, has facilitated the spread and establishment of many invasive species at higher latitudes . After aIn summary, climate change can alter the potential distribution of SAW. Global warming and adaptation to a wide range of temperatures allow the SAW to occur in regions outside its native range and move to higher latitudes, whereas the requirements of precipitation and intolerance to extreme heat cause a loss of its habitat in future conditions. Invasive crop pests can spread through natural and human means. In particular, human-mediated dispersals, such as international trade and travel, allow species to overcome long distances and geographical barriers to be introduced into non-infested areas globally; globalization is likely to exacerbate this problem . A previWe used the global occurrence records of the SAW and an optimized MaxEnt model to predict its potential geographical distribution under climate change. Our study concluded that the SAW has a widely suitable habitat outside its native range under the near-current climate, and it is expected to become wider in the future, although its distribution is restricted. Annual precipitation is the most important bioclimatic variable affecting the potential distribution of the SAW. The spatial distribution of the potentially suitable habitats will span a wider latitudinal range under climate change in the 2030s and 2050s. In summary, the SAW poses a threat to agricultural development in native and invasive regions, and environmental changes exacerbate this situation. Invasion hotspots, such as Australia, southern China, the EU, and other countries that are not yet invaded but are suitable for the SAW should adopt scientific quarantine measures to prevent the entry of this pest.


Patients with Peters anomaly are more likely to develop glaucoma as anterior segment dysgenesis progresses, and the effect of TLO is limited if corneal staphyloma is present.Glaucoma secondary to Peters anomaly is an important factor affecting visual prognosis, but there are few reports on the condition. This study aimed to investigate the characteristics of glaucoma associated with Peters anomaly and glaucoma surgery outcomes. This retrospective study included 31 eyes of 20 patients with Peters anomaly. Peters anomaly was classified into three stages: Stage 1, with a posterior corneal defect only; Stage 2, a corneal defect with iridocorneal adhesion; and Stage 3, a corneal defect with lens abnormalities. The associations between glaucoma and anterior segment dysgenesis severity, visual prognosis, and glaucoma surgery outcomes were analyzed. Sixteen eyes of ten patients developed glaucoma. Stage 1 Peters anomaly had no glaucoma, 52% of Stage 2 had glaucoma, and 75% of Stage 3 had glaucoma. Of the 16 eyes with glaucoma, 11 underwent surgery. Eight of these eleven eyes achieved intraocular pressure (IOP) control. Five of the nine eyes that underwent trabeculotomy (TLO) succeeded, and none had corneal staphyloma. Three of the four eyes for which TLO was ineffective had corneal staphyloma ( B3GLCT, PAX6, PITX3, FOXE3, and CYP1B1) has been reported to cause Peters anomaly. Notably, most cases of Peters anomaly are solitary; however, autosomal recessive and dominant inheritance patterns have also been reported [Peters anomaly is one of the causes of congenital corneal opacity and was originally described in 1906 by Dr. Alfred Peters, a German ophthalmologist ,3. The preported ,5. Homeoreported . Approxireported . The mecreported . In the reported . On the reported . PreviouIn this study, we reviewed the records of all patients diagnosed with Peters anomaly at the Department of Ophthalmology, Hiroshima University Hospital, between August 2009 and September 2021 and followed up for at least 6 months. The associations between glaucoma onset and the stage of anterior segment dysgenesis, visual outcomes, and postoperative results of glaucoma surgery were retrospectively examined. We collected data from electronic medical records, including age, sex, ocular findings, systemic findings, surgical course, and intraoperative and postoperative complications. This study was conducted according to the principles of the Declaration of Helsinki and was approved by the Institutional Research Ethics Committee (No. E2113). All treatment procedures also followed the principles of the Declaration of Helsinki.Peters anomaly was diagnosed clinically and classified as Stages 1, 2, or 3 according to the severity of anterior segment dysgenesis. Stage 1 was defined as the presence of a posterior corneal defect only; Stage 2 as a posterior corneal defect with corneal iris adhesion; and Stage 3 as a posterior corneal defect with lens abnormalities, including lenticulocorneal adhesion . RecentlThe diagnosis of glaucoma was based on IOP, changes in optic disc corneal diameter, and intraocular axis length. Cases in which the IOP was ≥21 mmHg on more than two occasions and those in which the corneal diameter or ocular axis length was increased were diagnosed with glaucoma . Most PeGlaucoma surgery was performed when the IOP was >21 mmHg or in cases of corneal diameter or ocular axis length increases. External trabeculotomy (TLO) was selected as the first-line surgery for glaucoma secondary to Peters anomaly, and trabeculectomy (TLE) with mitomycin and glaucoma drainage device (GDD) implantation was performed when TLO was ineffective. The surgical procedures were performed using previously described standard techniques ,14,15,16p < 0.05. All statistical analyses were performed using the JMP version 14 statistical package program .For statistical analysis, a log-rank test was used to determine the association between TLO outcomes and (i) the stage of anterior segment dysgenesis and (ii) corneal staphyloma. The Cochran–Armitage trend test was used to assess the association between glaucoma development and the severity of anterior segment dysgenesis. The Mann–Whitney U test was used to analyze the association between glaucoma and visual outcomes. Statistical significance was set at Thirty-one eyes of twenty patients were diagnosed with Peters anomaly. The median age at initial presentation was 0.88 years (interquartile range (IQR): 0.053–2.9 years), and the median follow-up time was 8.1 years (IQR: 5.6–9.1 years). The bilateral to unilateral ratio was 11:9, and seven patients were diagnosed with Peters plus syndrome , includip = 0.052; Sixteen eyes of ten patients developed glaucoma secondary to Peters anomaly. Of the sixteen eyes with glaucoma, none, thirteen, and three were classified as Stages 1, 2, and 3 Peters anomaly, respectively. Of the 15 eyes without glaucoma, 2, 12, and 1 were classified as Stages 1, 2, and 3 Peters anomaly, respectively. Stage 1 Peters anomaly had no glaucoma, 52% of Stage 2 had glaucoma, and 75% of Stage 3 had glaucoma. Secondary glaucoma did not occur in the eyes with Stage 1 Peters anomaly, and the incidence of secondary glaucoma tended to increase as the disease progressed . None of the five eyes that achieved IOP control with TLO alone had corneal staphyloma, whereas, among the four eyes where TLO was ineffective, three had corneal staphyloma (p = 0.0331). Among the three eyes with poor postoperative outcomes, two developed endophthalmitis after GDD implantation, and one did not achieve IOP control despite multiple surgeries.TLO was the initial surgery for nine eyes, and five achieved IOP control with TLO performed once or multiple times. Of the five eyes that achieved IOP control by TLO, three were classified as Stage 2 Peters anomaly, and two as Stage 3 Peters anomaly. In contrast, all four eyes that did not achieve IOP control with TLO alone were classified as Stage 2 Peters anomaly (Approximately half of patients with Peters anomaly develop glaucoma, and glaucoma secondary to Peters anomaly is an important complication that can affect visual prognosis ,7,10. InAdhesion between the lens and the cornea may occur as the severity of anterior segment dysgenesis increases. Previous studies said that the mechanism of glaucoma onset in Peters anomaly involves trabecular meshwork abnormalities or angle closure due to anterior segment adhesions. This result supported that a consequent anterior shift of the lens can cause angle closure, which may be involved in the development of glaucoma. Glaucoma secondary to Peters anomaly often develops in infancy, and all patients in this study were diagnosed with glaucoma on their initial visits. However, previous reports ,18 have In the existing literature, there are two reports on the treatment outcomes of glaucoma in Peters anomaly. Dolezal et al.  reportedIn childhood glaucoma, angle surgeries, such as goniotomy and TLO, are considered first-choice surgical procedures, with high success rates of 70–95% reported for primary pediatric glaucoma ,25. In cThe limitations of this study include its retrospective design, single-center setting, small sample size, and variable follow-up time. Moreover, there was no criterion in selecting the surgical technique for reoperation after the first TLO. The disease severity in this study was classified into Stages 1 through 3, but other papers used types 1 and 2, making it somewhat difficult to compare results because of the difference in severity classification. However, this study also has strengths. A single expert doctor specializing in pediatric glaucoma was involved in diagnosing and treating all cases, ensuring consistency in surgical procedures.In conclusion, Peters anomaly cases tend to develop glaucoma as anterior segment dysgenesis progresses. Therefore, careful follow-up of patients with Peters anomaly is necessary, especially those in Stage 3. TLO is effective for glaucoma secondary to Peters anomaly; however, its effectiveness may be limited to cases without corneal staphyloma.


I2 tests were used to measure the presence of heterogeneity. Thirty-seven randomized controlled trials were included , of which 23 were included in the meta-analysis. ICT interventions significantly improved Timed Up and Go (TUG) as a marker of physical mobility variable in older adults . A sensitivity analysis was performed on subgroups, and interventions were found to be effective in improving TUG in the exergame group  and in the exergame with virtual reality (VR) group  but both groups showed high heterogeneity. A meta-analysis was also performed on Short Physical Performance Battery (SPPB) but statistically significant results were not found . For the Berg Balance Scale (BBS), the post-intervention scores were significantly better than baseline . However, the number of studies included in the meta-analysis was small and heterogeneity was high, so follow-up studies are needed. This study confirmed that exergames, telecommunication, e-health, information applications, and robots were used as effective ICT-based interventions for improving the physical mobility of older adults. It is necessary to develop and apply more diverse ICT-based interventions that will prevent impairments of mobility and encourage older adults to live more independently, with a higher quality of life, based on extensive research on ICT-based interventions.Systematic literature review and meta-analysis were conducted to integrate and analyze intervention studies dealing with the effects of information and communications technology- (ICT-) based interventions on the physical mobility of older adults in the community. The PubMed/MEDLINE, Embase, CINAHL, and Cochrane CENTRAL databases were searched for studies published from January 2000 to December 2022. We used the Risk of Bias 2 (RoB 2) tool to evaluate the quality of the randomized controlled studies in the systematic review. The meta-analysis was performed using a random-effects model. The model was used to calculate the standardized mean difference (SMD) and 95% confidence interval (CI) for both effect measures.  The prolonged life expectancy and rapidly growing worldwide population of older adults have brought age-related physical, cognitive, and psychosocial health issues into the societal spotlight . Older aThe term “mobility” has various meanings depending on the context in which it is used . MobilitRecent advances in information and communications technology (ICT) have allowed the healthcare and medical sector to utilize the benefits of ICT in many ways, with impacts including reduced medical expenses, improved administrative tasks, maintaining patients' medical history, and reduced traditional paperwork . A reporVarious types of ICT-based interventions are performed to promote physical mobility, which has positive effects on older adults' quality of life . This stSystematic literature review and meta-analysis were conducted to verify the effects of ICT-related interventions on the physical mobility of older adults. This study was conducted according to the systematic literature review guidelines of Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) .Detailed data selection criteria were established as described below using PICO-SD, the key question strategy recommended in guidelines on systematic literature reviews . The parThree researchers who had experience in meta-analyses and literature searches conducted the literature search for this study after receiving IRB approval (IRB No. KYU-2020-145-01), and its protocol has been registered in PROSPERO (No. CRD42021225483).The search formula was created with a combination of terms representing the older population aged 65 and older (P) and ICT-based interventions (I). Four databases  were selected based on the COSI model suggested by the National Library of Medicine (NLM). Relevant full publications and conference abstracts were identified by electronic searching of the four online databases using both text words and exploded Medical Subject Heading (MeSH) terms: (aged) AND  AND (telemedicine OR information technology OR Information Science OR Robotics OR Video games OR Cell Phone OR Smartphone OR Mobile Applications). The results were limited to RCTs published in English between January 2000 and December 2022. In addition to the MeSH terms, text search terms were entered in the search. The detailed search formula is outlined in the Supplementary Material  for RCT studies developed by the Cochrane Bias Method Group . The RoBI2 index to quantify the dispersion among the studies. An I2 value of higher than 75% means considerable heterogeneity, 25% < I2 ≤ 75% indicates moderate heterogeneity, and an I2 value of 25% or less means low heterogeneity [d ≤ 0.50 denotes a small effect, 0.50 ≤ d ≤ 0.80 indicates a medium effect, and d ≥ 0.80 denotes a large effect [For studies that were suitable for meta-analysis, the effect size and homogeneity of the ICT interventions were calculated using R version 4.2.1. A meta-analysis was conducted when four or more studies reported data on the same outcome variable . Therefoogeneity . If the e effect . The funThis study reviewed the existing literature to identify the effects of ICT-based interventions on the physical mobility of older adults. The online database search yielded a total of 6,496 studies, including 2,493 from PubMed/MEDLINE, 1,719 from CINAHL, 2,154 from Embase, and 130 from the Cochrane CENTRAL. The number of overlapping studies from the first search was 2,131. Of the 4,365 studies, 50 were selected after applying the inclusion and exclusion criteria upon reviewing the titles and abstracts. Thirty-seven studies were finally selected for analysis, removing four studies that did not match the age criteria, three non-RCT studies, five studies that did not have eligible outcomes and research environment criteria, and one study that did not fit in terms of the intervention. 23 studies with measurements of the same variables were finally selected for the meta-analysis .The characteristics of the studies finally selected for the systematic literature review are presented in In the 37 selected studies, the number of participants in the intervention groups included in the analysis was 2,282 and the number of participants in the control groups was 1,996. The sample size ranged from 9 to 585 participants. Seven studies had a sample size of 15 or less in the intervention group , 56, 61,Details of ICT-based interventions are presented in Tables In the types of devices used in the ICT interventions (counting overlapping devices), personal computers , 62, 63 Telecommunications interventions mainly used telephones , 57, 64,The contents of the interventions were exercise in 19 studies , 67, 68,Individual interventions were performed in 30 studies , 63–68, The duration of the interventions ranged from 2 weeks to 48 weeks, and the weekly frequency of interventions (per week) ranged from 0.5 to 5 and 6 to 80 minutes per session. The highest proportion of interventions in 21 studies was self-performed using ICT, while others were performed by researchers in seven studies, or with third-party professionals including trainers, counselors, instructors, supervisors, or physiotherapists in 10 studies.The 37 studies used different variables to measure the physical mobility of older adults Tables  and 3. PBy intervention type, 18 studies used exergames, and the intervention group had 611 participants  including 353 females (except for those that did not report gender), compared to 589  in the control group, including 342 females. The sample size ranged from 9 to 372 participants in total , 68. TheIn terms of the contents of interventions, 12 studies provided exercise interventions , 59, 68,Each study suggested that it was effective to measure physical balance and function as a variable, with examples including gait speed , 44, 63,Three studies used exergames with VR, and the intervention group had 101 participants  including 10 females (except for those that did not report gender), compared to 41  in the control group, including 10 females. The sample size ranged from 24 to 60 participants in total , 34, 41.In terms of the contents of interventions, two studies provided exercise interventions , 41, andAmong the mobility variables measured in this study, TUG was most frequently reported to be significant in all three studies. It was confirmed that there was a significant improvement compared to the pre-test in the 10 m walk test and single-leg stance test, and significant changes were also reported in variables such as the Performance Oriented Mobility Assessment (POMA) , 41 and Six studies used telecommunication technologies for their interventions , 64, 67.In terms of the contents of interventions, two studies provided exercise interventions , 67, thrThese studies demonstrated effectiveness in terms of improving single leg stance (SLS), medial-lateral foot center of pressure (ML-COP), and TUG scores  and incrThree studies performed interventions by providing information using web-based communication technologies , 43, 65,Two studies provided motivation for exercise , 65, oneDelbaere et al.  demonstrTwo studies used applications , 66 and In terms of the contents of interventions, all studies provided motivation for exercise and presented health or nutritional advice. The interventions were self-conducted by the participants in two studies , 66 and Regarding outcome variables, inconsistent results were reported for gait step—namely, Bickmore et al.  reportedRobotic technology was used in two intervention studies, and the intervention group had 29 participants , compared to 26 (13 participants each) in the control group. The sample size ranged from 27 to 58 participants in total , 56. OneWearable devices were used in one intervention study , where pThe exercise interventions were provided for 60 minutes/session and 3 times/week for 12 weeks. The study reported that the Chair-Stand-30 (CS-30) scores and other physical function outcomes (TUG and CS-30) improved in both the intervention and control groups, but there was no statistically significant difference between the groups.The 37 publications were evaluated for their risk of bias using Microsoft Excel tool in accordance with RoB 2, provided by the Cochrane Group. In the first area of the randomization process, 16 studies (42.1%) were evaluated as low risk because they followed the randomization process relatively well with a detailed outlining of the randomization process and hiding the assignment order, while 21 studies (55.3%) were evaluated as having some concerns because they did not detail the process of randomization . One stuIn terms of the intended interventions, 28 studies (76.3%) were evaluated as low risk because they included statistical information on participants who were excluded from the intended intervention or dropped out but had a small impact on the outcomes. Three studies (7.9%) were evaluated as high risk because 5% or more of the participants were excluded from the analysis. Seven studies (15.8%) were evaluated as having some concerns about carrying out a modified intention-to-treat protocol because they included all participants except for those with missing outcomes or it was unclear whether the participants or researchers were aware of the randomization.The evaluation of missing outcome data estimated that three studies (7.9%) had some concerns because the dropout rate of the initial participants was 5% or more, and all others were evaluated as low risk. For measurements of the outcomes, seven studies (18.4%) had some concerns because a double-blind study was not conducted; thus, the outcome assessors may have been aware of the interventions that the study participants received. There was deemed to be a low risk of bias for the reported results .p=0.005, I2 = 74.7%, Q = 75.08, p < 0.001).Of the 37 studies, 20 used TUG as an outcome variable , 67, 68.I2 = 74.7%, VR with exergame I2 = 91.1%)  . To asse= 91.1%) .p=0.375, I2 = 87.7%, Q = 32.43, p < 0.001).Of the 37 studies, six used SPPB as an outcome variable. A meta-analysis was performed of five studies with a verified effect size , 63, 64,p=0.004, I2 = 93.5%, Q = 76.43, p < 0.001).Of the 37 studies, six used BBS as an outcome variable. A meta-analysis was performed of five studies with a verified effect size , 49, 68,t = −0.846, p=0.408; Begg rank correlation: Z = −0.649, p=0.516), Egger's test, Begg's test, and funnel plots did not identify any publication bias. The studies with SPPB  did not show any publication bias in Egger's test and Begg's test, but the funnel plot appeared asymmetrically, so publication bias could not be ruled out. However, studies with BBS  may have been subjected to potential publication bias  pandemic. Among the various types of interventions, exergames were used in 18 studies, accounting for almost half , followed by telecommunications, one of the most traditional types of ICT . This is in line with the results of previous systematic literature review studies suggesting that exergames are commonly used as an effective intervention for promoting physical activities or mobility among older adults , 69, 70.This study also found that telecommunications-based interventions, as a type of classic ICT, were cost-effective in boosting physical mobility among community-dwelling older adults. This conclusion is supported by another study that found telephone counseling to be effective in encouraging moderate physical activity , 57 and Interventions that used computer games and gaming devices for cognitive training exclusively or in combination with exercise interventions were effective for improving physical mobility , 61, 62.In particular, with the recent development of VR technology, VR exergames have been introduced. Compared to regular exergames, VR allows greater immersion in the situation, thereby increasing interest , 34, 41.Variables for measuring the physical mobility of older adults included measures of primary outcomes, such as physical activity , MVPA, etc.), physical performance , muscle mass and strength , balance , etc.), and gait performance , step count, 6MWT, etc.). In the meta-analysis, it was difficult to analyze the integrated effect size across the studies due to the inconsistent mobility measurement variables. 21 out of the 37 selected studies reported TUG as an outcome variable, and a meta-analysis was performed on the 20 studies in which the effect size could be confirmed. ICT interventions were found to be effective in improving TUG as a physical mobility measurement variable. A sensitivity analysis was performed for each subgroup, and the exergame and exergame with VR groups showed high heterogeneity, but TUG decreased from the pre-test to the post-test, proving that it was effective.In addition, a meta-analysis was performed on SPPB and BBS. For BBS, the post-intervention effect was significant. However, the number of studies used in the meta-analysis is small and heterogeneity is high, so follow-up studies are needed. Although TUG, SPPB, and BBS are widely used clinical assessment tools to evaluate balance and walking ability among the older adults, the concept of mobility in the elderly is a complex concept , so a toThis study is meaningful in that it verified the effects of ICT-based interventions on the physical mobility of community-dwelling older adults through a systematic and objective integration of individual studies. Most of the studies included in the analysis had a low risk of bias, and only RCT studies were included to ensure credibility. However, this study had limitations in that it only included studies published in the English language. In addition, this study included interventions with a small sample size (15 or fewer participants) , 56, 61 Most of the studies excluded from this study dealt with ICT interventions provided to older adults, focusing on rehabilitation from certain conditions, including dementia, stroke, and Parkinson's disease, as well as patients who had undergone musculoskeletal surgery, implying the need for further research on developing and expanding ICT-based interventions effective for promoting mobility among healthy community-dwelling older adults. Additionally, this study included interventions conducted in 22 countries distributed across five continents. Each country has different levels of digitalization and different levels of informatization, and these characteristics may affect the themes or effectiveness of interventions due to the level of development of the information society . TherefoThis study systematically reviewed research on the effects of ICT-based interventions on physical mobility among community-dwelling older adults and conducted a meta-analysis to determine the effect size of TUG, SPPB, and BBS, a variable for measuring physical mobility in older adults. The outcomes demonstrated that ICT interventions using exergames, e-health, information applications, and robots were effective in enhancing senior physical mobility, as well as telecommunication interventions . Moreover, ICT interventions were effective in enhancing physical mobility. In the future, more diverse ICT-based interventions should be developed and provided to older adults in the community to prevent impairments of mobility and cognitive function and to encourage older adults to live more independently, with a higher quality of life, based on extensive research on ICT-based interventions.


COVID-19 pandemic has changed people’s lives around the world due to restrictive measures adopted by governments. The impact of this change on female sexuality needs to be further investigated, particularly between female doctors who are more at risk as they are directly involved with health care services.An online survey has been filled out by female doctors. The questionnaire evaluates sexual function, depression, anxiety, burnout, sociodemographic and professional data, and it was answered during the peak of COVID-19 pandemic in Brazil. The main outcome is female doctors’ sexual function during COVID-19 pandemic, which was evaluated by analyzing FSFI questionnaires. The secondary outcome is related to their mental health, assessed via depression, anxiety and burnout questionnaires.A sample of 388 female doctors filled out the questionnaire. The median age was 34.0  years old. The total FSFI median score was 23.8  with desire domain median of 5.0 . In our sample, 231 (59.5%) women had depression and/or anxiety, out of these, 191 (82.7%) had depression and 192 (83.2%), anxiety. From these samples of doctors with depression and/or anxiety, 183 (79.2%) had sexual dysfunction.This finding suggests that doctors are experiencing a high risk of sexual dysfunction and mental illness during the COVID-19 outbreak. A high index of depression and/or anxiety was shown in the studied population, with almost 80% of them reaching criteria for sexual dysfunction. Working in the frontline is related to worse mental health conditions. Depression and anxiety were found as potential mediators of burnout effect on sexual function. From December 2019 onwards, the world has been facing the coronavirus disease (COVID-19), and since March 2020, the World Health Organization (WHO) declared the COVID-19 outbreak as a pandemic. Clinical manifestations vary from asymptomatic infections to a severe respiratory disease  with median desire domain of 5.0 . Approximately 72.2% (282) of women scored less than 26.6 in the FSFI, indicating they likely met diagnostic criteria for Female Sexual Dysfunction (FSD), in this group, 79.2% also met criteria for anxiety and/or depression .To better evaluate association among the presence of psychiatric diseases with FSFI score and controlling for confounding, linear regression models were made .β = -3.09, 95% CI , Model 2: β = -2.47, 95% CI ). Noteworthy, even in full adjusted model, significance was present .In all models, fulfilling criteria for a psychiatric disease presented a significant negative association with FSFI, specially on model with best fit , presented a significant negative association with FSFI total score. This association was lost in fitted model . In addition, in the adjusted models to practice physical exercises regularly  and maintaining sexual intercourse in the four previous weeks  presented a positive significant impact on sexual function measured by FSFI. In all models, variance inflation factors (VIFs) were below 2, pointing to absence of collinearity.In model 2, age equal to or greater than 40 years . It can be seen overall moderate and positive correlation between GAD and PHQ questions and scales. Depressive mood and tiredness presented significant moderate correlations with all GAD-7 scores .Also, "difficulty to relax" (question 4—GAD) presented a strong correlation with depressive mood, tiredness, feeling guilty and worthlessness and concentration problems. The item 3 (“To be worried about many things”) presented a strong correlation with difficulty to relax.In FSFI scores, we analyzed correlations on the total score of each dominium. Pain during intercourse was not correlated with GAD and PHQ scores in this sample. Desire presented a negative correlation with questions related to anhedonia, tiredness, suicidal thoughts, getting easily upset and the feeling that something terrible will happen. Total score of arousal, lubrication, orgasm and satisfaction also presented a significant negative moderate correlation with most of GAD-7 and PHQ-9 scales.Burnout was also assessed by the total score of each domain and a significant positive correlation was observed with scores of depersonalization and emotional exhaustion with GAD-7 and PHQ-9.Between depersonalization and emotional exhaustion was also observed a significant and a negative correlation with arousal, lubrication, orgasm and sexual satisfaction domains in FSFI scale. In contrast, when assessing personal accomplishment, there is a negative correlation with GAD-7 and PHQ-9, and a positive correlation with desire, arousal, lubrication, orgasm and sexual satisfaction.2/df = 1.838, RMSE 90% CI = 0.047 [0.04–0.053], p-value = 0.797 and SRMR = 0.063). In order to improve fit and convergence of the model, based on modification indexes over 10, we added covariances among questions 1 and 2 of PHQ, and first three items of GAD. Covariances between lubrication and orgasm, pain during intercourse and satisfaction, pain during intercourse and desire from FSFI were also added. The final model presented an excellent fit .At start, only covariance of anxiety and depression was included, fitting a reasonable fit  and anxiety . In contrast, depression  presented a significant negative effect on sexual function while anxiety a non-significant positive effect on sexual function. Covariance among anxiety and depression has also been significant   .(6) and 25.8 in women in childbearing age from Poland [In this survey, female doctors’ sexual function was mediated for depression and anxiety during COVID-19 pandemic. In our data, we have found a prevalence of sexual dysfunction of 72.7%, higher than the prevalence found among Chinese doctors before the pandemic, which was 49.7% in females . The medm Poland , possiblNoteworthy, 49.2% of this population achieved criteria for depression by PHQ-9, commonly used to screening participants , which iBurnout was positively correlated with anxiety and depression, with higher indexes of burnout scale between participants with mental illness. During the lockdown, the work environment became atypical and dealing with new protocols and patients significantly increased the rates of burnout and anxiety  while prWorldwide, COVID-19 epidemic and the restrictive social distancing measures have negatively influenced the sexual function and quality of life in noninfected reproductive-age women who live with their sexual partners . HealthcWorking in the frontline was an independent risk factor to worse mental health outcomes in all dimensions of interest in the study population. It was already reported that causes can vary, but for those in the frontline in particular, a lack of opportunity to adequately rest and sleep is likely related to an extremely large load of work, and a lack of personal protective equipment or training may exacerbate mental health impacts .Our findings have a great importance considering that the COVID-19 pandemic has not ended yet. Sexuality and mental health are closely related, and this research instigates a concern with the quality of life of health workers.The data presented must be considered within its limitations. This is a cross-sectional study, aiming to explore the problem in a specific population. There was no sample size calculated and participants were recruited via digital media and social networks, meaning that we were unable to identify respondents and non-respondents, which can lead to a biased sample. Unfortunately, we have no data collected from this population for a before and after comparison. During the COVID-19 pandemic, many professionals left their houses to avoid family contamination, and this was not considered.In conclusion, a high index of depression and/or anxiety was shown in the studied population, with almost 80% of them reaching criteria for sexual dysfunction. Depression and anxiety were found as potential mediators of burnout effect on sexual function. However, it is difficult to dissociate the effect of social restriction measures, longer working days, since these factors may be related both to psychiatric diseases and sexual dysfunction. Even so, promoting a lighter work and home environment can be the first step in the promotion of sexual satisfaction and a decrease in depression and anxiety rates during the COVID-19 pandemic for female doctors.Having found a high prevalence of sexual dysfunction and mental illness reinforces the importance of reassessing this population after the pandemic. As doctors are professionals who deal with the population, their sexuality and mental health must be a concern. It is of great importance to take care of their sexual health, improving their quality of life and global satisfaction.S1 TableModels described on (DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S1 Data(XLSX)Click here for additional data file.S1 File(DOCX)Click here for additional data file.


Hyperuricemia increases morbidity and mortality in type 2 diabetic individuals. It is linked to the expansion of diabetes and cardiovascular diseases indicators, as well as being a significant predictor of coronary artery disease. It also leads to a poor prognosis and increment of diabetic complications including diabetic neuropathy, retinopathy, and nephropathy. Therefore, this systematic review and meta-analysis was aimed to determine the pooled prevalence of hyperuricemia among type 2 diabetes mellitus patients in Africa.2 statistics. Publication bias was assessed through the examination of a funnel plot and Egger’s test. The pooled prevalence was estimated using a random effect model. Furthermore, sub-group and sensitivity analyses were conducted.We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. To identify relevant articles, we searched electronic databases such as PubMed, Google Scholar, African Journal Online, Science Direct, Embase, ResearchGate, Scopus, and Web of Sciences. The quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Statistical analysis was performed using Stata 14.0 software. To evaluate heterogeneity, we utilized Cochran’s Q test and IThe overall pooled prevalence of hyperuricemia among type 2 diabetic patients in Africa was 27.28% . The prevalence was highest in Central Africa 33.72% , and lowest in North Africa 24.72% . Regarding sex, the pooled prevalence of hyperuricemia among female and male type 2 diabetic patients was 28.02%  and 28.20% , respectively.This systematic review and meta-analysis showed a high prevalence of hyperuricemia among type 2 diabetic patients. So, regular screening and diagnosis of hyperuricemia required for preventing its pathological effects and contribution to chronic complications of diabetes.: PROSPERO (2022: CRD42022331279).The online version contains supplementary material available at 10.1186/s12902-023-01408-0. Diabetes mellitus (DM) is a group of heterogeneous disorders with multiple etiologies characterized by a chronic hyperglycemia resulting from defects in the insulin secretion and/or insulin action . AccordiType 2 diabetes is characterized by impaired insulin secretion by pancreatic cells or a failure of tissues to respond to insulin . It is tHyperuricemia is a condition in which a person’s serum uric acid (UA) level is abnormally high. In normal metabolic processes, UA is a byproduct of the breakdown and metabolism of purine substances . It is aIn T2DM patients, it is linked to the expansion of diabetes and CVD indicators, as well as being a significant predictor of coronary artery disease , 15. TheHyperuricemia has several side effects that have been linked to diabetic nephropathy. Endothelial dysfunction, enhanced renin-angiotensin-aldosterone system activity, and stimulation of inflammatory pathways, as well as pro-fibrotic cytokine activation –21, haveThis systematic review and meta-analysis was conducted in compliance with the guidelines provided by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) . The focTo ensure a thorough investigation, a team of four reviewers  conducted an extensive literature search. Major electronic databases such as PubMed, Google Scholar, African Journal Online, Science Direct, Embase, ResearchGate, Scopus, and Web of Sciences were utilized to locate relevant articles. Additionally, the proceedings of professional associations and university repositories were screened. To include any potentially overlooked studies, a direct Google search was performed using the bibliographies of the identified studies. The search spanned from February 2, 2022, to April 20, 2022.To optimize the search process, MeSH terms and a combination of key terms derived from the review question were employed. The following key terms were used in various combinations: “hyperuricemia, hyperuricemia, uric acid disorders, serum uric acid level, type 2 diabetes, non-insulin-dependent diabetes, insulin resistance, and Africa.“ These key terms were used individually as well as in conjunction with the Boolean operators “OR” and “AND” as necessary. Furthermore, the search was expanded by combining the aforementioned search terms with the names of all African countries.The final meta-analysis included observational studies conducted in Africa that met specific criteria and reported the prevalence of hyperuricemia among individuals with type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis included original articles published in peer-reviewed journals or grey literature, specifically those published in English. The studies needed to report the prevalence of hyperuricemia as their primary outcome, and they were considered up until April 20, 2022.We excluded qualitative research studies, review articles, case reports, narrative reviews, conference abstracts lacking complete information or where authors did not respond to our request for full-text, editorials, commentaries, letters to the editor, author replies, and other publications that did not provide quantitative information on the prevalence of hyperuricemia. Additionally, studies specifically focused on type 1 diabetes mellitus were also excluded.After conducting searches using electronic databases, conference proceedings, and bibliographic search, the articles were imported into EndNote version 20 software. Duplicates were then eliminated. Two independent reviewers (EA and AG) thoroughly examined the title, abstract, and full-text quality of each selected paper, adhering to the predetermined eligibility criteria. In cases where there was a disagreement between the two reviewers, a third reviewer (TF) was involved in resolving the discrepancy through discussion. The final selection of articles for the review was determined through this collaborative process.The selected papers underwent a thorough evaluation, and relevant information was extracted and summarized using a Microsoft Office Excel extraction table. This systematic review and meta-analysis were reported according to the preferred reporting items for systematic review and meta-analysis (PRISMA) guideline . To asseThe prevalence findings regarding hyperuricemia were independently extracted by three reviewers . The Microsoft Excel sheet was structured with subheadings agreed upon by all reviewers. The extracted data were meticulously cross-checked by the three reviewers, and any disagreements between the data extractors were resolved through discussions and consensus verification. The data extracted from each study included the first author’s name, publication year, country, sub-region, year of the study, study design, sample size, number of male and female participants, number of positive cases, prevalence of hyperuricemia, and the number of hyperuricemia cases by sex of participants.2 statistics were utilized. Heterogeneity was considered significant when the I2 test statistic exceeded 50% [The data were extracted into Microsoft Excel and subsequently imported into STATA 14.0 software for statistical analysis. To evaluate the heterogeneity between studies, Cochran’s Q test along with its respective p-value and Ieded 50%  and wheneded 50% . The resA total of 856 published articles were accessed through database searches and other sources. 222 articles were removed because of duplication. Then, about 634 articles were screened for their title and abstract, and 611 articles were removed. A total of 23 full-text articles were screened for eligibility criteria. Then, 09 full-text articles were excluded from the analysis for various reasons. Finally, 14 studies were included in this systematic review and meta-analysis for the final analysis  of them were in East African countries (3 from Ethiopia and 1 from Kenya) –30, 4  and Q test   to 45% . In random-effect model analysis, the overall pooled prevalence of hyperuricemia among T2DM patients in Africa was 27.28% . There was a high level of heterogeneity with I2 of 73%, 85.7%, 93%, and 92.4%, respectively ), followed by East Africa ), West Africa ), and North Africa ). A high level of heterogeneity was seen in all sub-regions with I2 of 56.0% and 78.2%, respectively  and 28.20%  respectively. A high level of heterogeneity was observed in both cases with I2 of 73%, 84.9%, and 95%, respectively ), followed by Ethiopia ), and Nigeria ). There was a high level of heterogeneity with I2 of 94.6%, 77.4%, and 79.4%, respectively ), and the lowest ) in 2007–2011. There was a high level of heterogeneity with ISymmetry of the funnel plot Fig.  and the Sensitivity analysis was performed to evaluate the effect of individual studies on the pooled estimated. When individual study was omitted, the pooled prevalence obtained was within the 95% CI of the overall pooled prevalence. This confirms the absence of single study impact on the overall pooled effect size Table .This systematic review and meta-analysis was directed to estimate the pooled prevalence of hyperuricemia among T2DM patients in Africa. T2DM is a huge global public health concern and it has a lot of modifiable and non-modifiable factors . One of Hyperuricemia contributes to the different pathological mechanisms of diabetes and its chronic complications. Mechanisms include inhibiting insulin pathway, endothelial dysfunction, inflammation, oxidative stress, thrombus formation, and activation of the renin-angiotensin-aldosterone system . A meta-In this review, the pooled prevalence of hyperuricemia among T2DM patients in Africa was 27.28% . The possible cause of hyperuricemia in T2DM patients might be due to decreased excretion of UA, consequences from the diminished effect of insulin , and incThe finding of this study was lower than a study conducted in China, which reported that 32.6% of T2DM patients had hyperuricemia . However2 = 89.1%) observed in this study might be due to numerous reasons. It might be due to prevalence differences in sub-regions of Africa, country, year of publication, and sex of study participants. As the result, we considered post-hoc subgroup analyses by different features such as sub-regions of Africa, country, year of publication, and sex of participants. According to subgroup analysis by sub-regions of Africa, the random effect model revealed that the highest pooled prevalence of hyperuricemia was reported in Central Africa , and the lowest was in North Africa . In addition, subgroup analysis by country indicated that the highest pooled prevalence of hyperuricemia was reported in Cameroon , and the lowest was in Nigeria . The possible clarification for these inconsistencies might be related to the differences in the study participants, glycemic control status, cultural differences, cut-off values, number of studies, sample size, and genetic pattern.The high level of heterogeneity  and 28.20%  respectively. Moreover, the subgroup analysis by year of publication revealed that the pooled prevalence of hyperuricemia in 2012–2016  was higher than in 2007–2011 . This difference might be attributable to the above expiations. However, still, subgroup analysis revealed that the presence of high heterogeneity and some differences across groups may not be statistically trustworthy because of the CIs overlap.Moreover, this review has some strengths and limitations. It allows determining the current and true pooled prevalence of hyperuricemia among T2DM in Africa. We have performed subgroup analysis , and followed the PRISMA guideline appropriately, which is considered the strength of our study. Moreover, our meta-analysis has limitations, such as the occurrence of significant heterogeneity even after subgroup analysis, only articles published in the English language were included. Hence the results of this meta-analysis had substantial heterogeneity and there was some overlap of CIs in the subgroup analysis. Finally, it was not able to evaluate factors associated with the pooled prevalence of hyperuricemia.This systematic review and meta-analysis showed a high prevalence of hyperuricemia among T2DM patients. It sounds that regular screening and diagnosis of hyperuricemia required in T2DM patients for preventing its pathological effects and contribution to chronic complications of diabetes. Subsequent follow-up is also essential for reducing diabetes-associated mortality and improving the quality of life for an individual living with type 2 diabetes.Below is the link to the electronic supplementary material.Supplementary Material 1