Methods: Studies to determine PFO and Fatmax using indirect calorimetry with an arm exercise protocol for SCI patients were included after a systematic search. Other endpoints included study design, sample size, control group, demographic data, level of injury, physical condition, protocol, outcomes measured, and statistical findings. Results: Eight studies (n = 560) were included. The mean value of VO2peak was 1.86 L∙min−1 (range 0.75–2.60 L∙min−1) . The PFO ranged between 0.06 and 0.30 g∙min−1 . Two types of exercise protocol were found: arm cycle ergometer, and wheelchair propulsion with a computerized ergometer. Five studies used an incremental protocol ; the rest performed tests of 20 min/stage at three intensities. Conclusion: There are few existing studies measuring fat oxidation in SCI, many of which used small and heterogeneous samples. PFO was lower in SCI subjects when compared with non-injured people performing lower-limb exercise; however, comparing upper-limb exercise, people with SCI showed higher values.Background: The aim of this study was to summarize evidence on energy metabolism through peak fat oxidation (PFO) and maximum fat oxidation (Fat Spinal cord injury (SCI) is associated with increased prevalence of metabolic ,2,3,4 anAs shown in a classic study by Bauman et al., 1994 , a highe2peak), this will increase up to a certain point and then decrease, showing peak fat oxidation (PFO). The relative intensity at which PFO is reached is called Fatmax. Furthermore, other factors—such as sex, physical condition, or nutritional status—influence Fatmax during exercise [max have been largely associated with insulin sensitivity, metabolic flexibility, and reductions in metabolic risk factors [max during physical exercise can be an important predictor of cardiometabolic health in both healthy populations and those with various pathologies. To this end, exercise protocols have been developed to reliably determine PFO and Fatmax, providing reference values for specific populations [The energy required during exercise is provided by fat and carbohydrates, and there is a shift in the mobilization and utilization of these substrates as intensity increases . The fatexercise . PFO and factors ,19. For ulations . Howeverulations , considemax, and to analyze the protocols that have been used. The secondary objective was to examine the main characteristics of subjects with SCI  that are related to their ability to oxidize fat during physical exercise.Therefore, the primary objective of this paper was to review the existing studies on energy metabolism in people with SCI that measure PFO and FatThis review follows the recommendations of the PRISMA statement .max based on gas analysis through indirect calorimetry. Observational and intervention studies published in English and Spanish were included. The exclusion criteria were studies on wheelchair users that did not specify that at least 75% of the included participants had an SCI. Two independent reviewers screened the titles and abstracts retrieved by the search and excluded the studies that were not eligible. Twelve studies were retrieved in full text and, after reading them, eight were selected to be included in the review  approach was used to rate studies for eligibility . Therefoe review .max protocols were developed [The search was carried out in PubMed and in the Cochrane Trial Database. In addition, a reverse manual search was carried out on the references of the articles included in the review. The date of the last search carried out was 2 February 2022. The search was limited to articles published since 2002—the year in which the Fateveloped . Details2peak, PFO, Fatmax), and findings . The author of one of the studies [Two independent reviewers abstracted data from the full-text articles using a sample data extraction form. The collected data included study design, sample size, presence or absence of control group, demographic data , level of injury, physical condition , protocol used for the fat oxidation test, outcomes measured . The total population of all of the studies was 91 subjects of both sexes (84 men and 7 women) and >18 years old (range: 22 to 64 years). Of the total of 91 participants, 85 subjects with SCI were included—in some studies exclusively ,33,34,35Most of the studies classified their SCI participants according to the American Spinal Injury Association (ASIA) Impairment Scale (AIS) . The AISAll but one of the studies  reported2peak, and all except that of Kressler et al. (2012) [2peak was 1.86 L∙min−1, although the range was between 0.75 and 2.60 L∙min−1, where the lowest value corresponded to subjects with tetraplegia [Three of the studies were conducted on athletes competing nationally and internationally ,30,31 in. (2012)  also off. (2012) ,34. Thusraplegia .Two different types of exercise were found depending on the wheelchair exercise protocol used:Arm cycle ergometer: This can be synchronous  or asynchronous . Synchronous movement has been shown to be more efficient , althougWheelchair propulsion exercise: With a computerized ergometer ,42, on aThe included studies used arm cycle ergometer exercise with asymmetric movement ,33,34,352peak [Only five studies ,33,34,352peak ,30,31. T2peak .−1. The lowest rates corresponded to non-trained subjects with cervical SCI (0.06 g∙min−1) [2peak, so PFO could have been out of this range. The paraplegic subjects showed the highest PFO (0.28 g∙min−1) [−1) [Five of the studies included PFO data calculated from an incremental exercise test ,33,34,35g∙min−1) ,30,31 de−1) [−1) ,30.max data [2peak, respectively.Only three studies provided Fatmax data ,33,34, omax. In general, they show values below those observed in studies carried out in non-injured populations, although they are significantly better when compared with non-injured subjects who perform the same type of exercise. Nevertheless, due to the heterogeneity of the studies, it was not possible to perform a meta-analysis of the results.There are few studies that have analyzed the oxidation of energy substrates during exercise in people with SCI. In addition, very few offer accurate data about PFO and Fatmax (56 vs. 51% VO2peak) and a higher PFO relative to lean mass [Sex is a factor that influences the ability to oxidize fat during exercise. It is known that although men obtain higher absolute PFO, women seem to have a higher Fatean mass . To the ean mass ,31,32,33ean mass ,30,35, bThe level of injury determines which muscle groups are paralyzed and which corporal functions are impaired. Therefore, the ability to perform physical exercise will be different depending on the level of injury. People with cervical SCI present impaired respiratory function  and diffAccording to the AIS, five degrees of injury exist: A, B, C, D, or E, where A and B are characterized by the absence of voluntary motor activity below the level of injury. Therefore, it is important to describe the degree of injury in studies carried out on SCI populations, due to the metabolic and physiological implications ,11,47. I2peak than those with paraplegia [2peak among people with tetraplegia, high paraplegia, and low paraplegia, along with a moderate positive correlation (r = 0.66) between level of injury and VO2peak. These same differences in VO2peak were observed in the studies included in this review, with lower values in subjects with cervical SCI. Thus, the limited existing evidence shows that individuals with cervical SCI have an impaired ability to oxidize fat. However, there are no studies comparing cervical versus thoracolumbar SCI, nor complete and incomplete injuries, to determine whether the level and extent of injury affect fat metabolism during exercise.Likewise, higher and complete SCI are associated with greater muscular, respiratory, cardiovascular, and neurovegetative effects. People with tetraplegia will have a lower maximum heart rate and VOraplegia . Accordiraplegia ,49, thermax [2peak values (mean of 2.44 L∙min−1), and the highest VO2peak was 2.60 L∙min−1 in the only study without tetraplegic participants [2 values obtained through upper-limb protocols will be lower than those achieved with more global exercises [2peak, PFO, and Fatmax, which would allow training protocols to be adjusted to optimize fat oxidation and physiological adaptations to exercise.Physical condition is an important factor to consider, since it has an essential influence on PFO and Fatmax . In the icipants . It is iicipants ,52. Morexercises . Neverthmax test, which connects PFO and the intensity of exercise achieved [max according to the level of training and the type of exercise performed. It would be interesting to compare PFO and Fatmax in different modalities to optimize exercise programs for people with SCI. Nevertheless, despite the fact that it has been widely used in the general population [max point than those that performed a test at three fixed intensities [max test should be adapted in SCI populations to accurately determine PFO and Fatmax.In 2002, Achten et al. developed the Fatachieved . Many auachieved , treadmiachieved , or arm achieved . This hapulation , this prpulation ,33,34,35ensities ,30,31. H−1 in men; from 0.35 to 0.45 g∙min−1 in women) [−1) and at higher intensity (41 vs. 13% VO2peak) than the control group, despite the significant differences in VO2peak (1.45 vs. 2.10 L/min) and age (45.10 vs. 30.30 years). Later, and following the same approach, Jacobs et al. (2021) [−1 and a Fatmax of 50.7% VO2peak in subjects with SCI, which is closely matched to the values obtained for athletes; thus, the sample of this study was probably in a good physical condition. Martín-Manjarrés et al. (2021) [−1)—both in absolute values and relative to whole-body lean mass and upper-body lean mass. Moreover, these differences persisted even when adjusting for VO2peak and fat mass. Meanwhile, Knechtle et al. carried out three studies on athletes with SCI [2peak (2.35–2.61 vs. 4.45–4.57 L∙min−1) and PFO (0.24–0.29 vs. 0.64–0.70 g∙min−1) between groups. This can be explained by the differences in the volume of muscle mass involved in the exercise in each case [The absolute values of PFO observed in the SCI population of this review are far from those recorded in untrained, non-injured populations performing incremental tests on cycle ergometers (from 0.46 to 0.58 g∙minn women) . Similarn women) ,31,32,33. (2021)  showed awith SCI ,30,31, awith SCI , the athwith SCI ,31. Consach case , the lowmax [2peak, respectively, which did not offer a sufficient range of intensities to accurately locate the PFO point. In two of these studies, the highest fat oxidation occurred at the 55%VO2peak stage [2peak; in the other, it was at 75%VO2peak [2peak, suggesting that Fatmax was around that intensity. The other study by Kressler et al. (2012) [2peak, which is exactly where the PFO was obtained. This seems to indicate that the Fatmax is equal to or less than that value.The three studies that provide data regarding Fatmax ,33,34 inmax ,30,31 us%VO2peak . Neverth%VO2peak  also car. (2012)  again usmax in the SCI population according to the studies analyzed ranged from 34% to 56% VO2peak, although the studies that measured it with more precise protocols obtained values between 34 and 41% VO2peak [max values, due to the aforementioned limitations of the protocols used. Therefore, there is limited evidence on Fatmax values in SCI populations, since the intensity ranges were not sufficient to determine the PFO.In summary, the values of Fat VO2peak ,33. In tThis study has some limitations. The included studies generally had a small and heterogeneous sample . Moreover, the lack of homogeneity in the protocols used—in terms of both the samples  and the outcome measures—made it impossible to perform a meta-analysis. Nevertheless, a strong point of this review is that it provides a vision of the state of the art regarding the oxidation of energy substrates in people with SCI, and it highlights the need for more research focused on the factors that influence the metabolic changes that occur after SCI, as well as how these affect the oxidation of energy substrates during physical exercise.max in SCI are few, and most of them include small and heterogeneous samples. Similarly, few studies have used adapted Fatmax protocols, limiting the ability to accurately understand fat oxidation in these subjects during exercise. Factors such as LOI and degree of injury should be considered when carrying out future studies on the oxidation of energy substrates, along with the physical condition, the differentiation between sexes, and the use of validated and identical protocols between subjects with and without SCI. In general, PFO and Fatmax were higher in SCI patients compared to non-injured people when performing the same type of exercise with the upper limbs in both groups (even when fitness levels were lower in those with SCI). Nevertheless, non-injured people performing lower-limb exercise  showed higher PFO and Fatmax than SCI subjects . In this sense, knowing how the different energy substrates are used during exercise is useful to guide training and to adjust it according to the Fatmax values for this population, which would help to maximize the benefits obtained during training—especially with regard to metabolic and cardiovascular problems. More studies—differentiating by sex, age, level and degree of injury, physical condition (including fitness level), lifestyle, associated pathology, and other factors that influence the oxidation of energy substrates—are necessary in SCI patients.Metabolism during exercise has scarcely been studied in individuals with SCI. The existing studies that measure PFO and Fat


Prostate cancer (PCa) is one of the common malignant tumors of the urological system, and metastasis often occurs in advanced stages. Chemotherapy is an effective treatment for advanced PCa but has limitations in terms of efficacy, side effects, multidrug resistance, and high treatment costs. Therefore, new treatment modalities for PCa need to be explored and improved. Pueraria lobata (PL). Next, Cytoscape software was used to draw the interactive network diagram of “drug–active component–target pathway.” Based on the STRING database, the protein–protein interaction network was constructed. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes were applied for the genes. Molecular docking was used to visualize the drug–target interaction via AutoDock Vina and PyMOL. Finally, prognosis-related genes were found by survival analysis, and Protein Atlas was used for validation.  R language and GEO database were used to obtain differentially expressed genes for PCa single-cell sequencing. TCMSP, STITCH, SwissTargetPrediction, and PubChem databases were used to obtain the active ingredients and targets of AR, MIF, HSP90B1, and MAOA genes were highly expressed, and molecular docking analysis showed that representative components had a strong affinity with receptor proteins. Survival analysis found that APOE, CA2, IGFBP3, MIF, F10, and NR3C1 could predict progression-free survival (PFS), and some of them could be validated in PCa.  Four active components and 31 target genes were obtained through the regulatory network of PL. Functional enrichment analysis showed that PL played a pharmacological role in the treatment of PCa by regulating the metabolic processes of reactive oxygen species, response to steroid hormones, and oxidative stress as well as IL-17 signaling pathway, PCa, and estrogen signaling pathway. Single-cell data showed that AR, MIF, HSP90B1, and MAOA to regulate several biological processes and related signaling pathways to interfere with the occurrence and development of PCa. APOE, CA2, IGFBP3, MIF, F10, and NR3C1 were also important as target genes in predicting PFS. In this paper, a drug–active ingredient–target pathway network of PL at the single-cell level of PCa was constructed, and the findings revealed that it acted on genes such as  Prostate cancer (PCa) is one of the common malignant tumors of the urinary system, and nearly 1.3 million new cases of PCa and 359,000 related deaths were estimated worldwide in 2018, ranking second and fifth in incidence and mortality rates of cancer in males, respectively [Pueraria lobata (PL) is one of the TCM. Liu et al. showed that extracts of PL could induce apoptosis in PCa cells by upregulating the expression of RASD1 and Bax [AKT, and CDK4 to induce cell cycle arrest in the G1 phase [Traditional Chinese Medicine (TCM) is a treasure house of potential drugs. Studies have shown that TCM has its unique advantages on the complex pathogenic mechanism of cancer. Therefore, the study of the mechanism of TCM may contribute to the development of a new combination of Chinese and Western medicine therapy . Network and Bax . In addiG1 phase . StudiesG1 phase , 9. HoweSingle-cell sequencing technology, which sequences the whole genome, transcriptome, and epigenome of individual cells, is significant in studying the differences and evolutionary relationships of the cell, revealing the complex heterogeneous mechanisms involved in disease onset and progression, and improving disease diagnosis, prognosis prediction, and monitoring of drug treatment effects , 11. Thihttps://www.ncbi.nlm.nih.gov/geo/) for inclusion in this paper. R language was used to define cell subsets according to marker genes, and cancer cell subsets were defined by copy number variation (CNV). Differentially expressed genes (DEGs) were obtained by FindAllMarkers function. DEG screening conditions were as follows: differential expression change fold change (FC) of mRNA, ∣logFC | >1, and adj. P < 0.05.Thirteen cases of PCa single-cell RNA sequencing data in GSE141445 were obtained from the GEO database (https://old.tcmsp-e.com/tcmsp.php). The screening conditions of active ingredients were as follows: oral bioavailability > 0.30 and drug‐likeness > 0.18. STITCH (http://stitch.embl.de/), SwissTargetPrediction (http://www.swisstargetprediction.ch/), and PubChem databases (https://pubchem.ncbi.nlm.nih.gov/) were used for complete PL composition target. The UniProt database (https://www.uniprot.org/) was used to transform IDs, and the final drug target was obtained after merging and deleting duplicates.The active ingredients and corresponding targets of PL were obtained using the TCMSP database  pathway was further obtained through the target gene. On this basis, the drug component–target gene pathway network was constructed and visualized through Cytoscape. Topological parameters of the network are obtained through “CytoNCA” plugin of the Cytoscape software.https://string-db.org/) for target genes, medium confidence > 0.4, and the results were visualized by Cytoscape.Gene Ontology (GO) and KEGG analyses were performed using clusterProfile, enrichplot, and ggplot packages in R language with PvalueCutoff = 0.05 and qvalueCutoff = 0.05 as the screening conditions. The results were presented as bubble plots. Protein interactions were analyzed by the STRING database (https://pubchem.ncbi.nlm.nih.gov/). The PDB files of the molecular structures of the target proteins were obtained using the RCSB PDB database (https://www.rcsb.org/). PyMOL and AutoDock Tools software were used to dehydrate, hydrogenate, and delete the original ligand of the target protein, save it as a pdbqt file for the receptor, and save the mol2 file of PL active ingredient as a pdbqt file for the ligand. The center of the binding pocket is centered on the ligand, which contains the smallest possible area for the ligand to bind, and was obtained by analysis with AutoDock Tools software. Molecular docking was achieved by the AutoDock Vina software, using the Vina force field for optimisation and binding energy calculations. Docking parameters are as follows: exhaustiveness is 8, and num_modes is 9. Root mean squared deviation (RMSD) analysis was performed on the docking results, and interaction pattern analysis was performed using PyMOL.The coordinate mapping diagrams of target gene expression at the level of cell clusters were obtained by the FeaturePlot function of R language. The mol2 files of the active ingredients of PL were obtained using the PubChem database . Progression-free survival (PFS) was analyzed by the univariate Cox proportional risk analysis and Kaplan–Meier analysis. Gene expression was analyzed by Student's t-test. From the online database Protein Atlas (https://www.proteinatlas.org/), the immunohistochemical microscopic images of genes were obtained and exported for visualization using image processing software Adobe Illustrator. The specific flow is shown in R language was used to obtain the data of 494 patients with PCa with complete clinical and transcriptome data from the cBioPortal database . The Kaplan–Meier survival analysis obtained APOE, CA2, F10, IGFBP3, MAOB, MIF, NR3C1, PLA2G2A, and SNCA differed in PFS (P < 0.05), but ABCG2 and PTGS2 showed no statistically significant difference in PFS (P > 0.05)   was the main driver of tumor cell genesis and development. It was activated and translocated to the nucleus to bind to androgen response elements in DNA and recruit regulatory factors or transcription factors that mediated target gene transcription to regulate biological processes such as cell proliferation, apoptosis, migration, invasion, and differentiation [MIF can promote PCa growth and metastasis by upregulating MAPK and CXCR7 expressions, thus activating the PI3K-AKT signal transduction pathway [AR, MIF, HSP90B1, and MAOA, as the targets of PL, exerted antitumor effects by regulating related pathways, suggesting that PL can interfere with tumorigenesis and progression through multicomponent, multitarget, and multipathway mechanisms. In addition, molecular docking experiments showed that the active monomers of PL had a spatial conformational docking effect with the proteins of the four corresponding target genes with good docking scores/binding energy, suggesting that PL may affect the protein activity and the regulation of its downstream pathways by directly binding to the active centers of the proteins. APOE, CA2, IGFBP3, MIF, F10, and NR3C1 were obtained for the prediction of PFS in PCa by the univariate Cox proportional risk analysis and Kaplan–Meier survival analysis of target genes. Protein Atlas verified that APOE, MIF, and NR3C1 were expressed in tumor tissues at different levels. The findings suggested that PL may intervene in the clinical prognosis of PCa by acting on the corresponding targets.Based on marker genes, nine cell populations were obtained, including cancer cells, to explore the potential role of PL in the treatment of PCa at the single-cell level. ntiation –28. Our  pathway . HSP90B1 pathway . In addi pathway , 32. MAO pathway –35. AR, This study may provide clues to the search for potential therapeutic targets and drugs for prostate cancer and refine our understanding of the efficacy of Pueraria lobata and its active ingredients. The limitation of this study is that the components of herbal medicine are complex and diverse in their therapeutic effects, and it is uncertain which combinations are at play, and more evidence is needed.AR, MIF, HSP90B1, and MAOA genes regulated several biological processes and related signaling pathways to interfere with the occurrence and development of PCa while its action on APOE, CA2, IGFBP3, MIF, F10, and NR3C1 genes was also important in interfering with clinical prognostic regression. The multiple drug–active component–target pathway axis constructed in this paper provided a new direction for exploring the therapeutic and prognostic targets of PCa. The above results were initially validated in molecular docking experiments and Protein Atlas, and the specific related molecular mechanisms need to be investigated further through experiments.In this paper, the drug–active ingredient–target pathway network of Chinese herbal medicine PL was constructed at the single-cell level of PCa by network pharmacology combined with single-cell sequencing technology. The findings revealed that its action on


Pancreatic cancer is one of the deadliest solid malignancies. Its surgical resection is technically very challenging and has a high risk of complications even after discharge. This study analyzed the risk factors associated with unplanned readmission after pancreatic cancer surgery.  Pancreatic cancer patients who were readmitted within 30 days after surgery were classified as the observation group, while those not readmitted within 30 days postsurgery were classified as the control group. The serum levels of gastrointestinal hormones, stress hormones, and peripheral immune cells of the two groups were compared at different intervals.  No significant differences in gender and age were observed between the two groups. At 7, 14, and 21 days postsurgery, the levels of gastrointestinal hormones motilin, gastrin, calcitonin gene-related peptide, and growth hormone-releasing peptide of the observation group were lower than the control group, while the levels of adrenocorticotropin, renin, angiotensin, and plasma aldosterone of the observation group were significantly higher than the control group. In addition, compared to the control group, lower levels of CD4+T cells, CD8+T cells, and NKT cells and higher levels of Treg, Breg, and MDSC cells were observed in the peripheral blood of the observation group.  The serum levels of gastrointestinal hormones, stress hormones, and peripheral immune cells could be associated with the risk of unplanned readmission within 30 days after pancreatic cancer surgery. Pancreatic cancer is one of the deadliest human cancers  and has Previous studies have shown that postoperative nutritional imbalance was associated with the postoperative death of approximately 10% of pancreatic cancer patients , 8. FurtRecently, unexpected readmissions after surgery have become a focus of attention for measuring the quality of care . ReadmisCurrently, research on the causes of unplanned postoperative readmissions in patients with pancreatic cancer is limited. In this study, we examined the factors associated with 30-day postoperative readmission in pancreatic cancer patients who underwent pancreatic surgery.The data of patients who were diagnosed with pancreatic cancer and underwent pancreatic cancer surgery at the Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology  from February 2019 to March 2020 were retrieved. Patients were selected based on the following inclusion criteria: ① The diagnosis of pancreatic cancer was made based on the guidelines for diagnosis and treatment of pancreatic cancer published by the Ministry of Health in 2011 ; ② the pTo assess the gastrointestinal function, stress response, and immune status of the patients, their corresponding serum hormones levels, i.e., motilin (MTL), gastrin (GAS), calcitonin gene-related peptide (CGRP), growth hormone-releasing peptide (Ghrelin), adrenocorticotropin (ACTH), renin (R), angiotensin (AT-II) and plasma aldosterone (ALD), cluster of differentiation (CD) 4+T cells, CD8+T cells, natural killer T cell (NKT), regulatory T cell (Treg), regulatory B cell (Breg), and myeloid-derived suppressor cell (MDSC), were investigated. The gastrointestinal function and stress response-related hormones levels were measured using enzyme-linked immunosorbent assay (ELISA). The immune cells were detected by Beckman Coulter CytoFLEX flow cytometry. All hormones were measured before surgery, and 7, 14, and 21 days after surgery. Briefly, 3 mL of the patients' peripheral venous blood was collected at the indicated time and the gastrointestinal, stress response, and immune related parameters were measured using ELISA or Beckman Coulter CytoFLEX flow cytometry.χ2 test. The measurement data were expressed as mean ± standard deviation (SD), and the comparison between groups was performed using the independent sample t-test. P < 0.05 indicated that the difference between comparisons was statistically significant.The Statistical Package for the Social Sciences  software was used for statistical analysis. Categorical variables were expressed as frequency and percentage (%), and the comparison between groups was expressed by the n = 41] and control group [n = 46]) pancreatic cancer patients were eligible for this study. In the observation group, there were 23 males and 18 females. They were from 44 to 69 years old and had an average age of 57.06 ± 10.25 years. In the control group, there were 24 males and 22 females. They were from 45 to 70 years old and had an average age of 57.74 ± 10.64 years. There was no significant difference in the general data between the two groups (P > 0.05).A total of 87 (observation group [P < 0.05).The hormones MTL, GAS, CGRP, and Ghrelin secreted by the gastrointestinal tract were measured to reflect the gastrointestinal function. As shown in P < 0.05; In this study, the hormones, ACTH, R, AT-II, and ALD, associated with stress response were measured. Our results showed that there was no significant difference in serum stress hormone levels between the two groups before surgery, but the levels of ACTH, R, AT-II, and ALD in the observation group were significantly higher than the control group at 7, 14, and 21 days after surgery (Here, the levels of CD4+T cells, CD8+T cells, NKT cells, Treg, Breg, and MDSC were measured to reflect the patients' autoimmune status. As shown in Tables In this study, we found that the serum levels of gastrointestinal hormones, stress hormones, and immune cells between the observation and control group were well-balanced before surgery but changed significantly at different postoperative time intervals.Studies have shown that anomalies in the secretion of gastrointestinal hormones after cancer surgery are important factors that affect changes in gastrointestinal functions . The gasThe surgical procedure for pancreatic cancer is technically challenging and is associated with significant trauma. In addition, the postoperative period is prone to stress and hormonal disorders, and these patients require intensive postoperative care due to the high risks of complications . Stress Further, in this study, on the 7th, 14th, and 21st day after surgery, the levels of CD4+T cells, CD8+T cells, and NKT cells in the peripheral blood of the observation group were lower than those of the control group, while higher levels of Treg, Breg, and MDSC cells were observed in the observation group. Studies have shown that surgery is an invasive procedure associated with acute inflammation and immune responses that can increase the risk of postoperative complications . Ding etIn conclusion, this study findings showed that the serum levels of gastrointestinal hormones, stress hormones, and peripheral blood immune cells could be relevant factors associated with unplanned readmission within 30 days after pancreatic cancer surgery. To reduce the risk of readmission, personalized clinical nutrition interventions before and after surgery could be implemented to timely counteract malnutrition in these patients. To validate these findings, further investigations using a larger cohort of patients in prospective settings are required.


Intracranial atherosclerotic stenosis (ICAS) causes a series of neurological symptoms, such as vertigo, impaired consciousness, limb weakness, ataxia, dysphagia, ocular motility disorders, and visual impairment. With the improvement of people's living standards, there are higher requirements for nursing care. Nursing, as an indispensable part of medical care, is closely related to achieving the goal of patient's safety and the overall quality of nurses, quality of care, and nursing management methods.  To explore the effect of risk-centered diversified safety management in patients undergoing aortic stenting.  Eighty patients with cerebral infarction were selected and treated with percutaneous transluminal angioplasty and stent implantation (PTAS). Then they were divided into a control group (40 cases) with routine monitoring and an experimental group (40 cases) with risk-focused intervention of a diversified safety management model according to the mode of care. Patient satisfaction and blood index test results were compared after the intervention. P < 0.05). The levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PA1-1), and von Willebrand factor (vWF) in the experimental group were (13.5 ± 1.3) ng/mL, (60.1 ± 9.9) ng/mL, and (2.1 ± 0.2), respectively, which were substantially lower than those in the control group ((14.6 ± 2.4) ng/mL, (64.2 ± 10.7) ng/mL, and (2.8 ± 0.3)), respectively (P < 0.05).  Patients in the experimental group had 6 falls, 3 bed falls, 3 phlebitis, 4 tube slips, and 10 deep vein thrombosis, all significantly fewer than those in the control group. Thirty-eight patients in the experimental group expressed satisfaction with safe management, which was substantially better than the control group ( The risk-centered diversified safety management model can effectively reduce the probability of adverse events in patients, improve patient satisfaction with nursing services, and promote faster postoperative recovery, which has clinical application value. The primary cause of ischemic cerebrovascular disease and transient ischemic attack (TIA) in China is intracranial atherosclerotic stenosis (ICAS) , 2. The Currently, the main treatments for ICAS include pharmacological therapy, endovascular therapy, and intracranial and extracranial arterial bypass grafting. In recent years, endovascular treatment has gained attention because of its minimally invasive and rapid recovery characteristics, but the results of the SAMMPRIS study and the VISSIT study suggest that the incidence of the primary endpoint event (stroke and death within 30 d of enrollment) in the endovascular treatment group was 14.7%, which far exceeded the incidence of 5.8% in the drug group . As the Nursing, as an indispensable part of medical care, is closely related to the overall quality of nurses, nursing quality, and nursing management methods and is related to the achievement of patient safety goals , 14. In Therefore, 80 patients with cerebral infarction were selected for PTAS of the intracranial artery, and routine care and diverse risk-focused safety management were given during the procedure. The intervention lasted for one month, and the changes in the indicators after the intervention were recorded. The effects of the risk-focused diversified safety management in patients undergoing PTAS surgery of large arteries were compared and analyzed, hoping to provide reference values for its future clinical application.A total of 80 patients with cerebral infarction aged 18-75 years who received treatment in our hospital from January 2020 to May 2022 were selected. The two groups were divided according to whether the diversified risk-focused safety management mode intervention was carried out after PTAS. The control group (40 cases) received routine monitoring, and the experimental group (40 cases) received the risk-focused diversified safety management mode intervention. Inclusion criteria are as follows: I. Patients with cerebral infarction confirmed by CT or MRI diagnosis on admission; II. No serious heart, liver, or renal insufficiency; III. No rheumatic heart disease, atrial fibrillation, blood system, or autoimmune diseases; IV. No drugs affecting coagulation function within one month; V. No history of major brain injury or surgery and no history of active hemorrhagic disease; VI. Cerebrovascular DSA confirmed intracranial arterial stenosis ≥50%. Exclusion criteria are as follows: I. Patients with transient cerebral ischemia; II. Chronic complete occlusion or severe calcification of intracranial arteries; III. Stenosis or occlusion of the middle cerebral artery, distal anterior cerebral artery, and posterior cerebral artery; IV. Neurological dysfunction after severe stroke ] × 100%. Dstenosis refers to the diameter of the smallest vessel in the stenosis segment, and Dconstant refers to the diameter of the proximal artery in the stenosis segment. The measured rates of arterial stenosis were determined by two experienced neurointerventionists who read the films independently.DSA examination was as follows: most subjects underwent routine preoperative examination after admission. Food was forbidden four hours before surgery, and the patient was sent to the Cath lab for total cerebral angiography under local anesthesia. After a successful femoral artery puncture by the Seldinger method, a 6F arterial sheath was inserted, and angiography was performed on the aortic arch, internal carotid artery, bilateral common carotid artery, subclavian artery, and vertebral artery. At the same time, the front and side positions were continuously exposed until the veins were empty. For suspicious vascular lesions that could not be identified by conventional projection, multiangle angiography was continued. The WASID equation  was usedAll patients underwent percutaneous endovascular stent implantation (PTAS). Postoperative blood pressure management was that the systolic blood pressure was maintained for severe stenosis between 100 and 130 mmHg, and systolic pressure was maintained in patients with nonsevere stenosis between 110 and 140 mmHg. Clopidogrel 75 mg/d and aspirin 100 mg/d were given orally for 12-16 weeks, followed by aspirin 100 mg/d for continuous treatment.Recognition period. The cases of falling/falling in bed, deep vein thrombosis, accidental burns, medication errors, phlebitis, and qualified rate of transport and handover were recorded. All risk factors related to objective patient safety management during treatment were sorted, and inspection tables were constructed. The number of cases of projects related to objective patient safety management that occurred in each clinical department was noted in detail. Indicators related to the management of patient safety objectives were screened. The nursing risk management projects in technology, service, business, and management were comprehensively counted from the perspectives of human, machine, material, environment, and law.Evaluation Period. Questionnaires were issued, and statistical analysis was conducted on all risk management projects. The risk index (number of occurrences × severity × discovery) was determined. A score of more than 350 was classified as unacceptable risk, 100-349 as major risk, 35-99 as moderate risk, 10-34 as permissible risk, and 1-9 as negligible risk. According to the statistical results, the checklist and Plato were formulated, and the patient safety objective risk management items were determined according to rules 20 and 80.Coping period. From the management aspect, the first is to run the nursing risk assessment scale comprehensively. Four nursing risk assessment scales were constructed and improved, including the risk factor assessment record for preventing patients from falling/falling in bed, the risk factor assessment scale for preventing catheter slip, the risk factor assessment scale for preventing phlebitis, and the risk factor assessment scale for preventing deep vein thrombosis. Through trial, revision, training, pilot, comprehensive rollout, and other management means, a comprehensive assessment of patients was implemented, which aimed to reduce or eliminate the incidence of falling/falling in bed, catheter shedding, phlebitis, and other items that affect the patient safety objectives and effectively ensure patient safety. Second, all relevant systems, processes, standards, and plans were enhanced for the implementation of patient safety objectives, such as the establishment of management systems, processes, standards, and plans for preventing patients from falling/falling in bed, preventing patients from phlebitis, and preventing pipeline slippage and deep vein thrombosis standard operation instructions (SOPs). A patient safety management system and assessment standards were established, as did the core monitoring index and key department management monitoring index of the whole hospital inpatient safety management. The nursing work notification system and health education system of various patient safety objectives were optimized and implemented. The third is to strengthen and implement oversight. The system and standard for verification, supervision, guidance, and evaluation of special risk projects of nursing management departments at all levels were established. Continuous improvement of care quality was carried out through PDCA quality management tools. A hospital-level comprehensive CQI nursing quality management project was established to strengthen the implementation and implementation of patient safety objectives and ensure effective management. From the aspect of personnel management, the implementation of training work was strengthened, and training plans were improved. Systematic and comprehensive training and assessment of the newly built specifications were conducted to ensure unified mastery and consistent execution of the working standards. In terms of facilities and environment, various warning labels should be established and improved to ensure patient safety, such as antifall/falling in bed, careful sliding, careful stepping, careful breaking of road, careful use of sugar, turning over card, antiscald, anticatheter falling off, careful electric shock, high-risk drugs, easily confused drugs, and other safety management labels. In terms of articles, all kinds of safe and qualified articles were provided, including all kinds of disposable articles, sterile articles, and implanted articles. In terms of equipment, operation procedures, troubleshooting, and emergency plans were established for various instruments and equipment, and training was implemented in a planned way to ensure that the efficiency of all staff was 100%.Monitoring period. Risk project quality inspection standards and evaluation standards were developed, and comprehensive organizational inspection, supervision, and evaluation of nursing work were planned to carry out the risk management and implementation effect. A comprehensive summary of project risk management achievements was made. The existing deficiencies should be carefully analyzed, improved, and implemented to make continuous quality progress and ensure the unification of standards. The implementation of specific norms as well as the realization of key projects, important standards, key norms, homogeneous management, and implementation were also important.Filing Period. Through comprehensive implementation, patients' safety objectives were fully collected and sorted out, and successful measures and methods were consolidated. A series of nursing risk management project case collections and standard operation protocols (SOPs) were set up to solidify and implement the project. All nursing colleagues in the hospital were educated and warned to prevent risks and learn and improve together.Management effectiveness evaluation. A questionnaire survey was used to evaluate the satisfaction with safety management and other contents of inpatients one month after the intervention. The Inpatient Safety Management Satisfaction Scale was mainly developed according to the Inpatient Satisfaction Scale, relevant literature, and specific work practice and has good reliability and validity.Blood index test. Two-milliliter venous blood samples were collected on an empty stomach at 7:00 am before the intervention and after the intervention experiment. Plasma was separated by centrifugation within 1 h , and the upper plasma was divided into a 0.5 mL EP tube, which was numbered according to the collection date and stored in a low-temperature refrigerator at −70°C for examination.The detection principle was as follows: quantitative determination of target antigen levels was conducted by the ELISA double antibody sandwich method. The coated antitarget antigen-antibody was combined with the target antigen in the plasma to be tested, and the enzyme-conjugated antibody was added to form a complex, which reacted with the substrate to display color. The A value measured at 490 nm was proportional to the plasma antigen content to be measured. According to the corresponding standard point data, the standard curve was drawn in Excel, and the standard curve equation was established. The concentrations of tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PA1-1), and von Willebrand factor (vWF) in the samples to be tested were calculated by the standard curve equation. Normal plasma concentrations of tPA and PAI-1 are 1.0-12.0 ng/mL and L5∼45 ng/mL, respectively. The plasma vWF level was measured as its ratio to the standard plasma content, and the normal range was 60%-150% or 0.6-1.5.Patients were admitted to the intensive care unit directly after surgery and were given intensive care with continuous monitoring of several parameters and close observation of changes in vital signs. Blood pressure was measured every 5-10 min during the 24 hours after surgery, and once an hour after the blood pressure stabilized for 24 h. The patient's consciousness, pupils, speech and body movement, and the presence of severe headache were observed at any time, and the doctor was notified of any abnormalities to prevent complications.After Wingspan stenting, the puncture site is usually sutured intravascularly with a vascular suture, but the suture may fail due to the influence of the technique, and the arterial pulsation and color of the punctured limb should be noted. Therefore, the pulsation and skin color of the dorsalis pedis artery on the operated side should be closely observed, and the dorsalis pedis artery should be measured every 30 min for 6 consecutive times. If the pulsation of the dorsalis pedis artery is significantly weaker than that of the opposite side and the pain of the lower limb is obvious after the operation, and the skin color is cyanotic, it indicates the possibility of arterial embolism of the lower limb. No lower limb artery embolism occurred in this group, but there were two cases of bleeding at the puncture site.The application of postoperative anticoagulant drugs is directly related to the success or failure of surgery. The most dangerous postoperative complication is acute arterial occlusion, which is mainly caused by subplaque bleeding or secondary thrombosis after plaque rupture. Therefore, postoperative treatment with low-molecular weight heparin is routinely administered, and patients are given warfarin 0.4 mLq 12 h subcutaneously for 1 week, aspirin 100 mg, and plavix 75 mg orally according to the doctor's prescription after returning to the ward. During the period of anticoagulation, the clotting situation was closely observed, and the clotting time and prothrombin time were monitored after the operation. The skin mucosa was closely observed for bleeding spots or purpura, the color of urine and stool, and other organs for signs of bleeding.T test, and continuous indicator groups were compared by analysis of variance. P < 0.05 was considered statistically significant.Data were processed and analyzed by SPSS 22.0. The counting data were expressed as the rate (%), while measurement data were expressed as the mean ± standard deviation (P > 0.05)  .P > 0.05). In the experimental group, there were 6 falls, 3 bed falls, 3 phlebitis, 4 pipeline slippage, and 10 deep vein thrombosis. In the control group, there were 28 falls, 22 bed falls, 14 phlebitis, 10 pipeline slippage, and 24 deep venous thrombosis. The experimental group had remarkably fewer unsafe events than the control group, and the difference between the two groups was considerable (P < 0.05)  .P > 0.05). In the experimental group, 36 patients were satisfied with the hand hygiene of nursing staff and 35 patients were satisfied with the operation standard, while in the control group, 29 patients were satisfied with the hand hygiene of nursing staff and 27 patients were satisfied with the operation standard (P < 0.05).The results in P > 0.05). Thirty-eight, 35, and 37 patients in the experimental group were satisfied with safety education, medication safety, and safety reminders, respectively, while 30, 24, and 28 patients in the control group were satisfied with safety education, medication safety, and safety reminders, respectively, with considerable differences (P < 0.05).According to the investigation shown in P > 0.05). There were 38 patients in the experimental group who were satisfied with safety management, while there were only 27 patients in the control group who were satisfied with safety management, and the difference between the two groups was considerable (P < 0.05)  .P < 0.05).Blood test results showed no notable differences in blood tPA, PA1-1, or vWF between the two groups before postoperative intervention Figures –7. AfterIntracranial atherosclerotic stenosis (ICAS) is one of the major causes of ischemic stroke , 23, accPTAS of intracranial arteries can directly dilate the narrowed intracranial stenotic arteries and rapidly improve the blood supply to the brain tissue in the ischemic area, which has advantages that cannot be replaced by previous pharmacological antithrombotic therapy. In addition, many relevant clinical application studies have shown that it has good therapeutic effects and safety . With thP < 0.05), effectively reducing the risk of adverse events. In the process of contact with patients, etiquette service provided an effective way to express, and nurses' considerate and meticulous service was an effective way to improve service quality. The results showed that the experimental group was significantly better than the control group (P < 0.05). In addition, the overall satisfaction of patients in the experimental group with safety management was also much better than that of the control group, indicating that our risk-focused safety management measures were indeed effective.Preoperatively, we understood the detailed condition of the patient and took the initiative to introduce the advantages and purposes of this treatment to the patient and family members to reduce the pressure on the patient. After the operation, we closely observed the vital signs, paid attention to the arterial pulsation and skin color of the punctured limb, and prevented the occurrence of arterial embolism and bleeding in the lower limb. All are for routine anticoagulation drug therapy, including close monitoring of blood clotting, observation of blood pressure changes, adjustment of the speed of antihypertensive drugs at any time, observation of the patient's consciousness, pupils' speech, and limb movement; it is the use of prophylactic drugs to prevent the occurrence of cerebral vasospasm. In conclusion, early detection of changes in condition and notification to physicians for timely treatment are the keys to reducing complications and improving the success rate of surgery. In medical activities, nurses have the most opportunities to communicate and contact with patients, and the triviality and complexity of nursing operations increase the incidence of nursing risk events. After one month of safety management intervention, the probability of adverse events in the experimental group was much lower than that in the control group, and the difference between the two groups was considerable (The results show that the risk-focused diversified safety management mode can effectively reduce the incidence of adverse events in patients, improve patients' satisfaction with nursing services, and promote faster postoperative recovery of patients. However, due to limited conditions, the sample size included in this study was small, and there was no great difference in some indicators. In addition, due to the limited research time, long-term safety management intervention for patients cannot be achieved. Further research is needed. In conclusion, the risk-focused diversified safety management model can effectively improve the quality of nursing, promote patient rehabilitation, and has clinical application value.


Desulfotomaculum and Thermovirga (PW), and Marinobacter (SD). There was an inferred high microbial activity in the oil fields, with the highest abundances of (i) cofactor, (ii) carrier, and (iii) vitamin biosynthesis, associated with survival metabolism. Additionally, there was the presence of secondary metabolic pathways and defense mechanisms in extreme conditions. Competitive or inhibitory relationships and metabolic patterns were influenced by the physicochemical characteristics of the environments (mainly sulfate concentration) and by human interference (application of biocides and nutrients). Our worldwide baseline study of microbial communities associated with environments of the oil and gas industry will greatly facilitate the establishment of standardized approaches to control MIC.The objective of the current systematic review was to evaluate the taxonomic composition and relative abundance of bacteria and archaea associated with the microbiologically influenced corrosion (MIC), and the prediction of their metabolic functions in different sample types from oil production and transport structures worldwide. To accomplish this goal, a total of 552 published studies on the diversity of microbial communities using 16S amplicon metagenomics in oil and gas industry facilities indexed in Scopus, Web of Science, PubMed and OnePetro databases were analyzed on 10th May 2021. The selection of articles was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only studies that performed amplicon metagenomics to obtain the microbial composition of samples from oil fields were included. Studies that evaluated oil refineries, carried out amplicon metagenomics directly from cultures, and those that used DGGE analysis were removed. Data were thoroughly investigated using multivariate statistics by ordination analysis, bivariate statistics by correlation, and microorganisms’ shareability and uniqueness analysis. Additionally, the full deposited databases of 16S rDNA sequences were obtained to perform functional prediction. A total of 69 eligible articles was included for data analysis. The results showed that the sulfidogenic, methanogenic, acid-producing, and nitrate-reducing functional groups were the most expressive, all of which can be directly involved in MIC processes. There were significant positive correlations between microorganisms in the injection water (IW), produced water (PW), and solid deposits (SD) samples, and negative correlations in the PW and SD samples. Only the PW and SD samples displayed genera common to all petroliferous regions,  For manOne limitation of metagenomics through analysis of 16S rRNA gene amplicons  is the absence of information about the functional and metabolic capabilities of the evaluated communities . The preNevertheless, although those tools provide us with information that can predict and diagnose MIC problems, it is still far to thoroughly understand all the intricate interactions comprising MIC. Literature data are heterogeneous, and it is often not possible to find a common denominator that can explain the putative driving factors that may be influencing the community dynamics of distinct microorganisms in each environment. In addition, obtaining data related to microbial communities present in industrial infrastructure is limited due to logistic difficulties of access to facilities and sample collection in pipelines, submarine, and subsurface equipment . FurtherGiven that scenario, it is highly relevant to establish a standardized study methodology, so that it is possible to compile and analyze the bulk of information already published, since there are still many knowledge gaps regarding the microbial communities’ structure and dynamics in oil and gas infrastructure. Therefore, the present systematic review aimed to evaluate the composition and relative abundance of bacteria and archaea associated with MIC, as well as the prediction of metabolic functions present in different samples from oil production and transport systems worldwide.th May 2021, were retrieved. The study selection process was performed in three steps: (1) identification of records in Scopus, Web of Science, PubMed and OnePetro databases; (2) screening of documents; and (3) evaluation of eligibility and inclusion of selected studies.This systematic review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines . All recSupplementary Material 1.In order to identify the records, a text search evaluating all the documents in all the three databases was carried out, using adequate and standardized search patterns. The keywords searched for were: petroleum, crude oil, oilfield, oil, reservoir, pipeline, biocorrosion, microbiologically influenced corrosion, microbial corrosion, MIC, corrosion, metagenomics, and 16s rRNA. All keyword combinations and the Boolean operators are detailed in csv text file format, whereas those from OnePetro were manually exported . Using the script format_input.py , Excel spreadsheet files were generated for each of the three databases, including the following variables: Title, Year, Digital Object Identifier (DOI), Document Type, Language, and Author(s). The script identified records without DOI and removed those ones with identical Title or DOI.Identified documents were automatically exported from Scopus, Web of Science and PubMed in remove_duplicates.py . Besides the initial variables, the unified spreadsheet file was added with the variable Repository, which describes from which database the record was retrieved. Furthermore, when the same record was identified in more than one database, this information was maintained in the description. The documents were downloaded as pdf files by their DOIs using a software based on permissions of ICB/UFMG internal network. Inaccessible documents were categorized as Not Available (NA) whereas the documents without DOI were manually downloaded.Excel spreadsheet files of each database were unified, and duplicated records were removed using the script corpus or removed.The selection of studies was performed by Joyce Dutra (J.D.) and Rosimeire Gomes (R.G.) and the divergences were solved by Mariana Santos Cardoso (M.S.C.). The divergences were solved as follows: After obtaining the documents (J.D. and R.G.), selected and non-selected files were merged, and the discrepancies were identified. Thus, these divergent documents were separated in one spreadsheet and forwarded to the third reviewer (M.S.C.), who judged whether the document would enter or not. In case of doubt, there was a census in the group of authors to decide whether the document should be remained in the final Titles and abstracts of the documents were reviewed, and only studies related to both oil fields and metagenomic analyses were retrieved. All these studies were completely re-evaluated based on the eligibility and exclusion criteria related to collection area, sample type, and obtained results: inclusion and exclusion criteria are listed in The following data were extracted from selected documents: (i) sampling design, (ii) physicochemical characterization of samples, (iii) DNA extraction, amplification, and high-throughput sequencing features, and (iv) taxonomic composition  and relative abundance of microorganisms obtained by both 16S rRNA amplicon and shotgun metagenomics.In order to standardize the data, all analyses encompassing the relative abundance of microbial taxa in all samples were performed at the genus level .For data extraction, all archaeal and bacterial genera were considered, regardless of their originally described relative abundance or absence of this information (in case there was only the report of their presence). After data extraction, absolute and relative frequencies for each genus were calculated. Data analyses were carried out for each sample type separately . Each set of sample types was evaluated for each distinct world petroliferous region, following the United States Geological Survey classification : 1—FormeResults of analyses of shareability and uniqueness patterns were illustrated as Venn diagrams, which were built with Venn v1.10 R package . In the p ≤ 0,05). The Spearman correlation test and corresponding correlograms were performed using PAST v. 4.08 , which is a multivariate statistical analysis of ordination, was used to integratively explore all data. PCA summarizes the information of a very high number of original variables in a small set of statistical variables. In the current study, the interrelationships among sets of microorganisms were analyzed using the first two principal components (PC1 and PC2). After Hellinger transformation, data were analyzed by PCA, and visualized by two-dimensional scatter plots using ggplot2 v3.3.5 and factoextra v1.0.7 R packages .FASTQ file.The functional prediction analyses were performed on all the available 16S rRNA amplicon metagenomes. Initially, SRA (Sequence Read Archive) or similar codes of all samples of all the selected documents were retrieved, considering at least one access code for each sample . A total of 23 documents had to be discarded since the access codes were not provided. Therefore, all samples from a total of 35 documents were automatically extracted using the SRA-Toolkit  for thosFASTQ file to be treated as the same sample. For each unique FASTQ file, low-quality sequences were removed (–fastq_filter) and identical sequences were fused (–derep_fulllength), and all the resulting processed sequences were concatenated in a single FASTQ file. Using this single FASTQ file, singleton and chimeric sequences were removed, both without and with reference to the scripts –uchime_denovo and –uchime_ref, respectively, with the databases of SILVA alignments prepared with MOTHUR (https://mothur.org/wiki/silva_reference_files). Finally, operational taxonomic units or OTUs (–cluster_size) were generated in both FASTA and BIOM file formats.In case of having technical replicates in the samples, these were concatenated in the same p-value > 0.05 was used as a threshold to discard statistically non-significant correlation between metabolic pathways.Functional inference of metabolic pathways based on MetaCyc database  was perfSupplementary Material 5). Among the 547 documents retrieved, 69 articles were selected because they could be directly used to respond to the main question of our study “What is the composition of bacterial and archaeal communities putatively associated with MIC found at distinct locations along the process of oil producing and transporting systems worldwide?” (format_input.py script and the remove_duplicates.py removed duplicate records (59 articles), according to identical DOI or identical title, and six documents were not available and thus defined as Not available. The remaining 388 documents were then downloaded in pdf format. We found 309 original articles and 79 other types of documents , which were excluded.A total of 552 records from the Web of Science, Scopus, PubMed, and OnePetro databases were retrieved; and 99 documents without DOI from the Web of Science and Scopus databases were removed. The Initially, the remaining 309 documents were manually screened, based on their title, abstract, and entire documents. When necessary, the exclusion criteria described in After this initial screening, 207 documents were excluded since they did not meet these eligibility criteria. Despite the application of the inclusion and exclusion criteria, a total of 40 documents did not comply with these criteria in the data extraction stage. Thus, in the step of data extraction, they were excluded. A total of 7 articles considered important for the review, but which had not been found in the database search, were also included: these articles were identified from the bibliographic references of previously selected documents. Therefore, a total of 69 articles were included in our systematic review for data analysis and synthesis.Supplementary Material 6). IW samples were analyzed from seven petroliferous regions, comprising a total of 18 articles, whereas PW was the sample type with the highest number of samples, described in 41 articles and distributed in seven petroliferous regions. O and OW samples were analyzed in eight and nine articles, respectively. Finally, SD were characterized from 34 articles by both sample type and petroliferous regions.Data was extracted and analyzed for each petroliferous region and each sample type. This method allowed the intrinsic analysis of the microbial profile of each variable (sample types and petroliferous regions). The pie charts indicate the type and number of samples. PW—produced water, IW—injection water, BSSP—biofilm/sediment/sludge/pig, Oil—oil, and O/W—oil/water mixture. Petroliferous regions are indicated by: R1—Former Soviet Union, R2—Middle east and North Africa, R3—Asia-Pacific, R4—Europe, R5—North America, R6—Central and South America, R7—Sub-Saharan Africa and Antarctica, and R8—South Asia.To determine the composition of microbial communities and relative abundance of microbial lineages present in samples, the authors of selected documents extracted the community DNA and performed mainly amplicon (16S rRNA) metagenomics or, more rarely, shotgun metagenomics.Supplementary Material 7). Among the 69 articles, 57 used one of these methods, one (1) described its own methodology, six (6) referred to other authors, which are not included in the selected documents, and six (6) did not report the extraction method applied. The most cited methods in the selected articles were commercial kits (43) and the Maxwell automated platform (2). The articles mentioned commercial kits for DNA extraction from different sample types: soil (i); biofilm (ii); water (iii), and general (iv). In the present systematic review, the kits manufactured and indicated for DNA extraction from plants, animals, bacteria, algae and fungi were grouped and named “General”. The biofilm kits were used for SD samples, and the water kits for IW and PW samples. The TRIzol reagent was referenced by an article for extracting DNA from PW samples.A total of five methods of metagenomic DNA extraction were identified: (1) commercial kits; (2) TRIzol-based; (3) phenol-chloroform-based; (4) QuickGene semi-automated platform; and (5) Maxwell Automated Platform  and 1392R (5′-ACG GGC GGT GTG TRC-3′) were used to amplify the V6–V8 region of 16S rRNA genes from bacteria and archaea. Considering sample types, these primers were used for amplification in 27 of them: IW (4), PW (8), SD (13), and O (2).https://dna.macrogen.com/), and articles 245 (https://jgi.doe.gov/). Articles 42 (The articles reported Sanger (1st generation) and NGS (new generation) sequencing platforms. The Sanger method, carried out in the ABI PRISM 310, ABI PRISM 377, ABI PRISM 3730  sequencers, were described in six studies, while 454  was reported in 23 studies, and MiSeq  in 35 studies. Article 212  cited thcles 245  and 249 cles 245  mentioneicles 42  65  of biocides and other possibly interfering chemical products. Microbial communities are dynamic, and the conditions prevailing in the systems will determine the community structure.Supplementary Material 8). Among the included articles, 68.11% described the temperature, 63.77% the pH value, 56.52% the salinity, 68.11% the sulfate concentration, 28.98% the application of biocides and other chemical products, and 24.63% the nitrate concentration.Therefore, in order to perform these analyses, data related to sampling point, temperature, pH value, salinity, sulfate and nitrate concentrations were collected, as well as data regarding the application of biocides and other chemical products  of the ordination analysis (PCA) jointly explained approximately 40% of data variability . In addiSupplementary Material 9), Moreover, no statistically significant correlations were identified. The regions R4, R5 and R6 presented genera with high relative abundances (13.33–33.33%), and, among them, only the R5 region displayed statistically significant correlation.Regions R1, R2, and R3 showed the highest number of genera, with high shareability and uniqueness, and relative abundances below 3% (0.34–2.94%) . In the R5 region, five genera were also detected, three unique and two shared with the R3 region. The dominant genera in this region were Bacteroides, Synergistes, and Sedimenticola, with high relative abundances (16.67–25%) ; however, they are not known to participate directly in MIC processes. Moreover, the genera Bacteroides and Methylophaga were significantly positively correlated  , which justifies the proximity between these two regions . Nevertheless, the genera that most influenced data variability in this region were Halomonas (4.44%), Petrobacter (4.44%), Alcanivorax (4.44%), and Desulfovibrio (2.22%). There were statistically positive correlations between the nitrate-reducing bacteria (NRB) Halomonas and methanogens (MET) Methanolobus and Methanosaeta  and sulfate-reducing (Desulfotomaculum) functional groups.R3 region exhibited a higher number of exclusive genera . Additio0RB and APB) (0RB), (MET and APB) and genera of the G1 group  from the R2 region, with an abundance of less than 3.0%, aerobes of the class Alphaproteobacteria . Those genera with the highest relative abundance comprised Defluviitoga (4.07), Thermodesulfovibrio (4.07%), Pelotomaculum (4.07%), Desulfotomaculum (4.07%) .The R1 region was composed of 45 genera, with 13 unique to it . All of and APB) . Among tPetrobacter and Pseudomonas, which are NRB. Negative correlations were also retrieved between NRB and APB of the genera Pseudomonas and Acetomicrobium (2.33%), respectively, from the R1 region.The R2 region display important genera of the phylum Proteobacteria that correlated significantly and positively, such as Pseudomonas (a hydrocarbon-degrader NRB) and Methanosaeta (MET) with 1.61%, . Among the diverse genera that were identified, a total of 18.75% were constituted by genera of the class Deltaproteobacteria, which contains many SRB, and 18.18% of the phylum Euryarchaeota, in which all representatives are MET.The R3 region was composed of 322 genera, of which 172 were unique to it , and preArcheoglobus (5.00%); NRB, Arcobacter (2.73%); SRB, Desulfotomaculum (4.09%) and Desulfuromonas (3.64%); S0RB, Petrotoga (3.18%) and Geotoga (2.27%), . In addition, there were significant positive and negative correlations between some genera . These sulfidogenic genera (Desulfuromonas and Geotoga) were correlated negatively with the thermophilic and hydrogenotrophic methanogen Methanothermobacter, which was the one that most contributed to explain data variability in the R1 region. In turn, the genus Geotoga was also correlated with other genera, highlighting negative correlations with the thermophilic Thermoanaerobacter, an iron-reducing genera , Acetobacterium (4.86%), Desulfomicrobium (4.17%), Smithella (3.12%), Thermotoga (2.78%), Thermoanaerobacter (2.43%), and Proteiniphilum (2.08%) . The genera in this region were positively correlated , Desulfobacter, Caminicella, Mesotoga, and Dethiosulfatibacter . This region has statistically significant positive and negative correlations (Dethiosulfatibacter and Desulfobacter (Geotoga (S0RB) in the R4 region. Additionally, Dethiosulfatibacter and Desulfobacter were also negatively correlated with Marinobacter, a NRB that was dominant in the R7 region. The S0RB Caminicella was positively correlated with other S0RB genera in the R4 and R7 regions; and negatively with the thermophilic S0RB genera, the most relevant in the R5 region, as well as with thermophilic MET Methanothermobacter in the R1 region. The SRB Desulfovibrio, displayed significant positive correlations with NRB and other SRB genera that are resistant to pollutants, such as Sulfurospirillum from the R7 region , Petrobacter (3.06%), Methanobacterium (3.07%), Methanocalculus (3.05%) (Methanosaeta (3.32%), Spirochaeta (3.60%), Thermanaerovibrio (3.88%), Marinobacter (4.16%), Pseudomonas (4.16%), Methanolobus (4.43%), and Marinobacterium (4.71%) . Four groups of positively correlated genera were observed  and the SRB Desulfomicrobium, which was the most relevant in the R5 region. The second one comprised the MET Methanocalculus, and the hydrocarbon-degrader NRB Halomonas (R1) and Marinobacter (R7). The third one was composed of the MET Methanobacterium and the APB Acetobacterium (R1). Finally, the fourth one, which displayed correlation between the NRB Marinobacterium and the MET Methanoculleus, the most relevant in the R5 region, Methanosaeta and Methanolobus, the most relevant in this R7 region. Regarding the negative correlations, the genus Marinobacterium was correlated with the aerobic genus Massilia, which was the most relevant in the R1 region.The R7 region was composed of 84 genera, 11 of which were unique to it . The mos (3.05%)  and Methobserved  and 4C. In the present study, 25 O samples and 36 OW samples were analyzed; and both did not exhibit genera that were statistically significantly correlated . In the Amphibacillus, Clostridium, Enterococcos, Serratia, and Staphylococcus . In the R3 region, 14 genera were considered those that most contributed to the ordination of this region; however, the genera with the highest relative abundance were Ralstonia, Burkholderia, Sediminibacterium, and Pseudomonas  .The R2 region , had a glococcus . These c0RB was observed. On the other hand, in the R7 region, only one genus that influenced the data variability was highlighted, Marinobacter (NRB), with a relative abundance of 4.58%. Regarding the analysis of shareability and uniqueness, this region exhibited 50 genera with 40 unique ones  exhibited an abundance below 3.0% . In the R3 region, 29 genera were described, and 25 of them were unique  as the most abundant genera. The R5 and R7 regions were relatively close to each order in the ordination analysis when compared to the other regions .The regions R2 and R3  were fare unique . Nine gee unique , includi regions . These rGeobacter and the SRB Desulfovibrio . In the R7 region, 23 genera (of which six unique ones) were described (Pelobacter e Acetomicrobium) NRB (Marinobacter e Marinobacterium), thiosulfate-reducing bacteria—TRB, and S0RB , as well as a smaller number of SRB were also detected, as well as in the R5 region .The R2 region (group b) was segregated from all the other regions in the ordination analysis , and shoobacter,  and the rrelated . On the Pseudomonas (2.78%), followed by the IRB Shewanella (2.20%), and APB, such as Proteiniphilum (2.22%) .In the ordination analysis, the R3, R4, R5, R6 and R7 regions were relatively closer to each other than with R2 region . The R3 0RB and SRB), NRB, and MET, with greater abundance of Thermococcus and Desulfonatrospira (6.45%), followed by the Methanothermococcus (4.84%).The R4, R5, R6, and R7 regions displayed similar genera and shared many functional groups. The R4 region had 32 genera, of which six unique to it , with reMethanothermobacter and genera with an abundance above 3% in the NRB, APB, S0RB and IRB functional groups. In turn, the R5 region had 78 genera, 37 of which are unique (Pseudomonas (4.17%) as the most abundant, followed by Desulfomicrobium, Desulfovibrio, and Methanosaeta (3.65% each).There were statistically significant positive correlations between the MET e unique . The relMethanococcus and the APB Acetobacterium; and the second one between MET Methanolobus and Methanosaeta and the hydrocarbon-degrader NRB Pseudomonas. Furthermore, the later correlated positively with the most abundant genera in the R7 region: the MET Methanobacterium.The R6 region exhibited 17 genera, with two unique to it . This re0RB Thermanaerovibrio did not significantly correlate with the other genera. In the R7 region, there were positive correlations between genera within the region and with genera of the R4 region, which had an abundance greater than 3.0%. The MET Methanoculleus and Methanocalcullus correlated positively each other and also with Thauera (3.41%), anaerobic hydrocarbon degrader. The NRB Marinobacterium and the S0RB Kosmotoga were positively correlated with each other and also with APB Sedimentibacter. Moreover, Marinobacterium and Kosmotoga (3.23%) also correlated with genera of S0RB, APB, and MET groups in the R4 region . The S0RB Kosmotoga correlated with the APB Spirochaeta and Geoalkalibacter (3.23%) from the R4 region. Geoalkalibacter is strictly anaerobic, and there are species that can utilize Fe(III), Mn(IV), nitrate, elemental sulfur and trimethylamine N-oxide as terminal electron acceptors, and a wide variety of organic acids as electron donors. The most abundant genus is Methanobacterium (6.82%), followed by Methanolobus and Methanosaeta (5.68%). This region was dominated by the hydrogenotrophic methanogens Methanobacterium, Methanocalculus, Methanoculleus, and Methanosaeta.The R7 region had 58 genera, of which 15 unique to it , with reAmong the 16S rRNA metagenomes recovered from different sample types, a total of 440 metabolic pathways was identified in Metacyc at the highest classification level using PICRUSt2. Removal of statistically non-significant metabolic pathways (p ≥ 0.05) resulted in a total of 167 pathways, p < 0.05 are shown; G—pie chart of predicted functions and substrate types.Extended error bar graph was used for the comparison between two samples. The bar graphs on the left display the average proportion of each MetaCyc pathway, while the dot plots on the right show the differences in the average proportions between two samples: A—produced water (PW) and solid deposits (BSSP); B—injection water (IW) and produced water (PW); C—produced water (PW) and oil; D—injection water (IW) and solid deposits (BSSP); E—solid deposits (BSSP) and oil; F-injection water (IW) and oil. Only predicted functions with A pairwise comparative analysis of the metabolic prediction of the different sample types were carried out to identify the greater or lesser similarity between sample types and functional categories from the different petroliferous regions . Since PFor PW and SD, Nucleoside and Nucleotide Biosynthesis was the most expressive functional category, followed by Fatty Acid and Lipid Biosynthesis, Carbohydrate Biosynthesis, and Amino Acid Biosynthesis . The mosThis study evaluated the microbial profile of samples associated with the oil industry  in seven petroliferous regions, comprehending several countries all over the world. Many of these countries figure in the ranking of the top 15 oil producers in the world  and eachThe PW and SD sample types were the most numerous, with 155 (42.12%) and 119 (32.34%) samples, respectively, out of a total of 368. PW is one of the most common sources of microbiological samples , mainly Regarding molecular biology methods, we detected that 62.3% of the documents performed DNA extraction using commercial kits specific for each sample type. This is justified by the complexity of the material, as they may have elements that influence cell lysis, isolation of nucleic acids or polymerase activity . For DNA2 concentration, pH value, and salinity)  alters the diversity of microbial communities during oil production.Concerning the IW, PW and SD samples, the region R3 presented the smallest number of genera able to explain data variability  and 7C, Arcobacter, Pseudomonas, and Marinobacterium. The regions R6 and R7 were the closest ones, which suggests a higher similarity between the variables, sharing the genera Pseudomonas and Marinobacterium. The R4 also highlighted, exhibiting the Marinobacter genus, which is present in relative abundances above 2% in the R1 and R7 regions.In IW samples, the R6 region displayed the largest vector, indicating greater importance in explaining data variability, highlighting the genera Arcobacter participates in elemental sulfur oxidation, nitrogen metabolism, and iron and manganese reduction. Moreover, many studies suggest that these bacteria may not be native of oil reservoirs, but artificially introduced  in anaerobic conditions (The genus troduced . Bacteriservoirs . Pseudomentation  and capamixtures . On the naerobic  and consnditions .Arcobacter and Pseudomonas found more than 20 genes associated with antibiotic and biocide resistance. One of these genes was oprN (outer membrane efflux protein), which encodes a multidrug efflux pump related to glutaraldehyde resistance   as carbon and energy sources  . These grocesses  and are rocesses . This ge sources . Thermovcceptors . These gSupplementary Material 8).The greater distance of the R1 region when compared to the other regions indicates its unique features . This re0RB. There was also a high abundance of syntrophic and methanogenic archaea. Low concentrations or absence of sulfur compounds in PW may possibly decrease sulfate generation but do not prevent the development of microorganisms that are involved in the carbon cycle (such as fermenting or syntrophic bacteria)  .2 (electron) transfer between species . natronum . RegardiIn O samples, the distance between the regions indicates that each one presented a distinct microbial profile. Furthermore, the opposition between R3 and R6 suggests that they may be completely negatively correlated, and there are no shared genera between these regions. The R3 region was dominated by aerobic microorganisms, with the vast majority not known to directly participate in MIC, whereas the R6 region was dominated by microorganisms that are known to cause MIC (sulfidogens).Ochrobactrum and Acinetobacter, while at the wellhead of the other well, there was a higher abundance of genera such as Lactococcus and Pseudomonas. Among these genera, Pseudomonas is the most mentioned in oil fields, probably due to the water injection into the reservoirs, and by the fact its species are potential hydrocarbon degraders. Strictly aerobic species of the genus Sediminibacterium were isolated from a Chinese reservoir and display interesting characteristics, with species capable of producing hydrogen sulfide (H2S) and organic acids from sugars. Regarding the other genera, there is not much information related to their metabolism in the oil field; however, some species of these genera are aerobic or facultative anaerobes, antibiotic-resistant and are also considered pathogens, as well as important organisms in biotechnology.Archaeoglobus and Desulfovibrio and showed a high abundance of APB and S0RB, indicating that there may be a syntrophic relationship between these functional groups. Archaeoglobus and Desulfovibrio. The genus Archaeoglobus comprises hyperthermophilic sulphate-reducing archaea, frequently found in hydrothermal vents and oil wells, with temperatures around 85 °C, which develop in environments with high salinity , there were also differences between oil fields, which displayed very different microbial profiles. This region exhibited dominance of S0RB, APB, NRB, and hydrocarbon degrading genera. The high availability of nutrients, together with the probable decrease in pH due to the excess of byproducts of the metabolism of both APB (organic acids) and S0RB species (H2S), may have excluded SRB and MET. Moreover, sulfate unavailability may have been an important factor in the low abundance of SRB .R7 region had the lowest number of genera that explain data variability data . The higMarinobacter in all regions may indicate that this genus actively participates in the biochemical processes that occur in oil fields. The presence of hydrocarbon-degrading bacteria and biofilm-forming syntrophic bacteria allied to MET is expected to facilitate hydrocarbon degradation in oilfields, since it is likely that, while syntrophic bacteria degrade hydrocarbon substrates to products such as acetate, hydrogen or carbon dioxide, methanogens use these substrates to produce methane  with genera from the TRB group  may indicate that there is no competition between these genera and that the environment is providing necessary conditions for the development of both genera.The R2 region was contemplated by only one study , includiHalomonas, with facultative aerobes, nitrate-reducing, halophilic and alkane-degrading species, and the genus Methanosarcina, a methanogen that can use three metabolic pathways  to produce methane  may indicate inhibition by toxicity. Nitrite is an intermediary compound in denitrification by NRB, and , with a relative abundance of 66%, and this phylum has chemolithotrophic and anaerobic representatives. Furthermore, the authors only reported their results at the phylum level, and, thus, it was not included in our initial data analysis . The abundance of Flavobacterium may be due to the high availability of organic material rich in dimethyl sulfide (DMS) originated from the degradation of the compatible solute dimethylsulfonyiopropionate (DMSP). DMS can be co-metabolized, generating a flow of electrons that is probably used in energy metabolism and thus in biomass formation , such as adhesive exopolysaccharides, and these compounds promote the adherence of other microbial groups, establishing a cooperative relationship, in addition to promoting protection against biocides, disinfectants, and other environmental stresses  may indicate exclusion by toxic metabolites. As previously discussed, in the R2 region, NRB may release nitrite, which is toxic to methanogens, such as Methanosarcina, causing their inhibition . This region was dominated by hydrogenotrophic methanogens , commonly found in environments of low salinities and mesophilic temperatures. There was also the presence of methylotrophs, such as Methanolobus, which use methanol and methylamine to produce methane, which are not used by SRB  and secondary  ( others) .12 contain rare organometallic bonds, which are used by enzymes in a variety of central metabolic pathways, such as amino acid (L-methionine) synthesis  as end-products of their metabolism, which are used as substrates by the chemolithotrophic SRB and methanogenic bacteria and archaea, through the incomplete reductive tricarboxylic acid cycle (TCA) cycle pathway.The pairwise combination of sample types from the oil fields was also evaluated to biologically verify the statistically significant differences between the metabolic groups. The high number of statistically different pathways in the combination between PW and SD can be explained by the greater number of articles and samples obtained, which led to a greater number of 16S rRNA sequences for these sample types. Carbohydrate, amino acid, and nucleotide metabolism are associated with hydrolysis, the initial breakdown of complex compounds and substrates . In the Incomplete reductive pathways of the TCA cycle can still transform pyruvate into biosynthetic intermediates needed in response to anaerobic or microaerophilic growth conditions . Most an2. In IW samples, the statistical significance of this pathway was already expected due to the origin and processes of this sample type in oil fields, due to water injection in wellhead, creating an aerobic environment  in PW when compared to IW. Nevertheless, the presence of this metabolic pathway in both sample types was probably due to the recirculation of PW together with IW, which can promote contamination of organisms such as ronments .Lactococcus and Pseudomonas at the wellhead of an oil well with continuous injection of IW.In contrast, this metabolic pathway is less abundant in O samples and SD. Nevertheless, the explanation for their occurrence may be due to the pits along the pipelines, which can cause an aerobic microenvironment and permit the development of organisms with this kind of metabolism . AnotherThe microbial composition of oil fields in different sample types and petroliferous regions, along with the production and transport processes worldwide, showed that most of detected microorganisms are potentially involved in MIC processes . Furthermore, these microbial functional groups, jointly with nitrate reducers, probably established syntrophic or inhibitory relationships.Desulfotomaculum and Thermovirga genera in all petroliferous regions. Moreover, there was an emphasis on the syntrophic relationships between sulfidogens, methanogens, nitrate-reducing and acid-producing microorganisms. Otherwise, in SD samples, despite also presenting high diversity, a distinct microbial profile was observed: higher abundance of APB and NRB, and important syntrophic associations between sulfidogens, methanogens and NRB were retrieved. The latter group includes biofilm-forming organisms, such as Pseudomonas. In SD samples, the NRB Maribacterium was present in all petroliferous regions. Presence and abundance of these groups and correlations between them were influenced by environmental physicochemical characteristics, especially, sulfate concentration, as well as anthropic interferences, such as the application of biocides. High sulfate content favored the sulfate reduction metabolism by SRB, while in sample types with low sulfate content, there was a metabolic deviation of SRB, which probably ally with methanogens as a survival strategy. The application of chemical products caused several changes in the environment. In many cases this strategy is efficient in causing the inhibition of potential organisms involved in MIC (such as SRB), but it induced the selection of: (i) antibiotic resistant organisms, such as Pseudomonas, (ii) organisms whose metabolism uses the applied products (THPS) as substrate, such as Methanolobus, and (iii) organisms tolerant to extreme conditions, mainly high pH values, such as Halomonas, Methanobacterium, and Anoxynatronum, among others. Moreover, the petroleum environment was also rich in non-SRB sulfidogens, and these bacteria are probably not affected by common biocides. According to the functional prediction analysis, there are high microbial activity in oil fields, with the highest abundances of Cofactor, and Carrier, and Vitamin Biosynthesis, which plays the role of catalysts for essential reactions in microorganisms, such as the biosynthesis of carbohydrates and amino acids. Additionally, there was also the presence of secondary metabolic pathways, such as terpenoid biosynthesis and aromatic compounds biosynthesis, which are directly involved in survival, under stressful conditions as well as used as a defense mechanism.The PW and SD samples had the largest data volume and, thus, more consistent results were obtained from these samples. In PW samples, despite high microbial diversity, sulfidogenic groups were more abundant, with the presence of the Therefore, our worldwide systematic review and analyses of existing data in the specialized literature of microbial communities associated with environments of the oil and gas industry has generated a global scientific synthesis of this theme, which can greatly facilitate the establishment of standardized approaches to control microbial-induced corrosion.10.7717/peerj.14642/supp-1Supplemental Information 1Click here for additional data file.10.7717/peerj.14642/supp-2Supplemental Information 2This document explains 1. who are the two authors who performed the Search Strategy and identify them in our manuscript; 2. how disagreements were resolved, and identify the referee in our manuscript, 3. The rationale for conducting the systematic review / meta-analysis; 4. The contribution that it makes to knowledge in light of previously published related reports, including other meta-analyses and systematic reviews.Click here for additional data file.10.7717/peerj.14642/supp-3Supplemental Information 3Click here for additional data file.10.7717/peerj.14642/supp-4Supplemental Information 4All the information (metadata) from all the articles used in the Systematic Review, separated by distinct databases.Click here for additional data file.