Category: Statistics

Genome Med. 2021 May 17;13(1):85. doi: 10.1186/s13073-021-00902-1.

ABSTRACT

BACKGROUND: Single liquid biopsy analytes (LBAs) have been utilized for therapy selection in metastatic breast cancer (MBC). We performed integrative statistical analyses to examine the clinical relevance of using multiple LBAs: matched circulating tumor cell (CTC) mRNA, CTC genomic DNA (gDNA), extracellular vesicle (EV) mRNA, and cell-free DNA (cfDNA).

METHODS: Blood was drawn from 26 hormone receptor-positive, HER2-negative MBC patients. CTC mRNA and EV mRNA were analyzed using a multi-marker qPCR. Plasma from CTC-depleted blood was utilized for cfDNA isolation. gDNA from CTCs was isolated from mRNA-depleted CTC lysates. CTC gDNA and cfDNA were analyzed by targeted sequencing. Hierarchical clustering was performed within each analyte, and its results were combined into a score termed Evaluation of multiple Liquid biopsy analytes In Metastatic breast cancer patients All from one blood sample (ELIMA.score), which calculates the contribution of each analyte to the overall survival prediction. Singular value decomposition (SVD), mutual information calculation, k-means clustering, and graph-theoretic analysis were conducted to elucidate the dependence between individual analytes.

RESULTS: A combination of two/three/four LBAs increased the prevalence of patients with actionable signals. Aggregating the results of hierarchical clustering of individual LBAs into the ELIMA.score resulted in a highly significant correlation with overall survival, thereby bolstering evidence for the additive value of using multiple LBAs. Computation of mutual information indicated that none of the LBAs is independent of the others, but the ability of a single LBA to describe the others is rather limited-only CTC gDNA could partially describe the other three LBAs. SVD revealed that the strongest singular vectors originate from all four LBAs, but a majority originated from CTC gDNA. After k-means clustering of patients based on parameters of all four LBAs, the graph-theoretic analysis revealed CTC ERBB2 variants only in patients belonging to one particular cluster.

CONCLUSIONS: The additional benefits of using all four LBAs were objectively demonstrated in this pilot study, which also indicated a relative dominance of CTC gDNA over the other LBAs. Consequently, a multi-parametric liquid biopsy approach deconvolutes the genomic and transcriptomic complexity and should be considered in clinical practice.

PMID:34001236 | DOI:10.1186/s13073-021-00902-1

Clin Epigenetics. 2021 May 17;13(1):111. doi: 10.1186/s13148-021-01095-5.

ABSTRACT

Worldwide, colorectal cancer (CRC) is a deadly disease whose death rate ranks second among cancers though its incidence ranks third. Early CRC detection is key and is associated with improved survival outcomes. However, existing tests for CRC diagnosis have several weaknesses thus rendering them inefficient. Moreover, reliable prognostic tests that can predict the overall cancer outcome and recurrence of the disease as well as predictive markers that can assess effectiveness of therapy are still lacking. Thus, shifting to noninvasive liquid biopsy or blood-based biomarkers is vital to improving CRC diagnosis, prognosis, and prediction. Methylated circulating tumor DNA (ctDNA) has gained increased attention as a type of liquid biopsy that is tumor-derived fragmented DNA with epigenetic alterations. Methylated ctDNA are more consistently present in blood of cancer patients as compared to mutated ctDNA. Hence, methylated ctDNA serves as a potential biomarker for CRC that is worth investigating. In this review, we explore what has been reported about methylated ctDNA as a biomarker for CRC diagnosis that can distinguish between CRC patients or those having adenoma and healthy controls as validated specifically through ROC curves. We also examine methylated ctDNA as a biomarker for CRC prognosis and prediction as confirmed through robust statistical analyses. Finally, we discuss the major technical challenges that limits the use of methylated ctDNA for clinical application and suggest possible recommendations to enhance its usage.

PMID:34001239 | DOI:10.1186/s13148-021-01095-5

Stem Cell Res Ther. 2021 May 17;12(1):289. doi: 10.1186/s13287-021-02305-w.

ABSTRACT

BACKGROUND: Recent studies demonstrated that autologous mitochondria derived from bone marrow mesenchymal stem cells (BMSCs) might be valuable in the treatment of spinal cord injury (SCI). However, the mechanisms of mitochondrial transfer from BMSCs to injured neurons are not fully understood.

METHODS: We modified BMSCs by CD157, a cell surface molecule as a potential regulator mitochondria transfer, then transplanted to SCI rats and co-cultured with OGD injured VSC4.1 motor neuron. We detected extracellular mitochondrial particles derived from BMSCs by transmission electron microscope and measured the CD157/cyclic ADP-ribose signaling pathway-related protein expression by immunohistochemistry and Western blotting assay. The CD157 ADPR-cyclase activity and Fluo-4 AM was used to detect the Ca²⁺ signal. All data were expressed as mean ± SEM. Statistical analysis was analyzed by GraphPad Prism 6 software. Unpaired t-test was used for the analysis of two groups. Multiple comparisons were evaluated by one-way ANOVA or two-way ANOVA.

RESULTS: CD157 on BMSCs was upregulated when co-cultured with injured VSC4.1 motor neurons. Upregulation of CD157 on BMSCs could raise the transfer extracellular mitochondria particles to VSC4.1 motor neurons, gradually regenerate the axon of VSC4.1 motor neuron and reduce the cell apoptosis. Transplantation of CD157-modified BMSCs at the injured sites could significantly improve the functional recovery, axon regeneration, and neuron apoptosis in SCI rats. The level of Ca²⁺ in CD157-modified BMSCs dramatically increased when objected to high concentration cADPR, ATP content, and MMP of BMSCs also increased.

CONCLUSION: The present results suggested that CD157 can regulate the production and transfer of BMSC-derived extracellular mitochondrial particles, enriching the mechanism of the extracellular mitochondrial transfer in BMSCs transplantation and providing a novel strategy to improve the stem cell treatment on SCI.

PMID:34001228 | DOI:10.1186/s13287-021-02305-w

BMC Res Notes. 2021 May 17;14(1):186. doi: 10.1186/s13104-021-05598-5.

ABSTRACT

OBJECTIVE: African ancestry seems to be a risk factor for hypertension; however, few genetic studies have addressed this issue. This study aimed to investigate the prevalence of polymorphisms NOS3; rs1799983, IGFBP3; rs11977526 and TCF7L2; rs7903146 in Brazilian women of African descent and their association with hypertension.

RESULTS: The prevalences of the less frequent genotypes were 26.5% TT genotype of NOS3; rs1799983, 16.7% AA genotype of IGFBP3; rs11977526, and 18.3% TT genotype of TCF7L2; rs7903146. For these conditions, the prevalence of hypertension and PR (adjusted) relatively to the ancestral genotype were, respectively: 52.0% vs 24.5% (PR = 1.54; p < 0.001), 62.0% vs 24.1% (PR = 1.59; p < 0.001), and 38.9% vs 27.9% (PR = 0.86; p = 0.166). Associations with hypertension were statistically significant, except for the TCF7L2; rs7903146 polymorphism, after adjusted analysis. Brazilian Afro-descendant women with the TT genotype for the NOS3 gene and the AA genotype for the IGFBP3 gene are more susceptible to hypertension. The understanding of underlying mechanisms involving the pathogenesis of hypertension can motivate research for the development of new therapeutic targets related to nitric oxide metabolism and the management of oxidative stress.

PMID:34001234 | DOI:10.1186/s13104-021-05598-5

BMC Sports Sci Med Rehabil. 2021 May 17;13(1):53. doi: 10.1186/s13102-021-00280-6.

ABSTRACT

BACKGROUND: Basketball is the most popular sport in Lebanon. Adequate nutrition has been established to be a key component of optimal athletic performance, recovery from exercise and exercise-induced injury and documented to be associated with adequate nutrition knowledge (NK). In Lebanon, nutrition education is not incorporated into the basketball player training program and there is no established position for sports nutritionists in basketball clubs. To our knowledge, the present study is the first to evaluate the NK status of Division I Basketball (D1B) players /coaches in Lebanon. The objectives of this study are to assess the prevalence of inadequate NK; identify the gaps in NK, main sources of nutrition information, perceptions on sports nutrition and independent predictors of inadequate NK among D1B players and coaches in Lebanon.

METHODS: All D1B players (n = 184) and coaches (n = 16) in Lebanon were invited to participate in the study. Study participants were asked to complete a questionnaire that included questions on NK, resources and perceptions. A percentage of ≥60% of NK questions answered correctly was used as indicative of having adequate NK. Descriptive statistics were used to summarize the sample characteristics. The T-test and chi square test were used for comparisons of means and proportions, respectively. Logistic regression was used to explore the predictors of inadequate NK in D1B players.

RESULTS: The sample consisted of 178 D1B players (n_M = 126; n_F = 52) and 11 male coaches, resulting in survey response rates of 97 and 69%, respectively. Inadequate NK was found among about 80 and 54% of D1B players and coaches, respectively. Inadequate NK was found to be independently associated with lack of nutrition education in D1B players.

CONCLUSIONS: Despite widespread lack of adequate NK among D1B players and coaches in Lebanon, our sports clubs do not have dietitians. Basketball sports clubs in Lebanon should start to budget for hiring a dietitian or carrying out nutrition education campaigns that are based on analyses of incorrect responses of our study participants. Findings of this study are of tremendous significance to D1B players in Lebanon in terms of improving the athletes’ physical health and performance.

PMID:34001207 | DOI:10.1186/s13102-021-00280-6

Scand J Trauma Resusc Emerg Med. 2021 May 17;29(1):65. doi: 10.1186/s13049-021-00880-8.

ABSTRACT

BACKGROUND: Trauma is a leading cause of morbidity and mortality worldwide with about 5.8 million deaths globally and the leading cause of death in those aged 45 and younger. The pre-hospital phase of traumatic injury is particularly important as care received during this phase has effects on survival. The need for high quality clinical trials in this area has been recognised for several years as a key priority to improve the evidence base and, ultimately, clinical care in prehospital trauma. We aimed to systematically map the existing evidence base for pre-hospital trauma trials, to identify knowledge gaps and inform decisions about the future research agenda.

METHODS: A systematic mapping review was conducted first employing a search of key databases (MEDLINE, CINAHL, EMBASE, and Cochrane Library from inception to March 23rd 2020) to identify randomised controlled trials within the pre-hospital trauma and injury setting. The evidence ‘map’ identified and described the characteristics of included studies and compared these studies against existing priorities for research. Narrative description of studies informed by analysis of relevant data using descriptive statistics was completed.

RESULTS: Twenty-three eligible studies, including 10,405 participants across 14 countries, were identified and included in the systematic map. No clear temporal or geographical trends in publications were identified. Studies were categorised into six broad categories based on intervention type with evaluations of fluid therapy and analgesia making up 60% of the included trials. Overall, studies were heterogenous with regard to individual interventions within categories and outcomes reported. There was poor reporting across several studies. No studies reported patient involvement in the design or conduct of the trials.

CONCLUSION: This mapping review has highlighted that evidence from trials in prehospital trauma is sparse and where trials have been completed, the reporting is generally poor and study designs sub-optimal. There is a continued need, and significant scope, for improvement in a setting where high quality evidence has great potential to make a demonstrable impact on care and outcomes.

PMID:34001219 | DOI:10.1186/s13049-021-00880-8

Trials. 2021 May 17;22(1):346. doi: 10.1186/s13063-021-05293-7.

ABSTRACT

BACKGROUND: Up to three quarters of surgical patients receive inadequate pain relief, with 40% of patients reporting severe pain following knee replacement, which may indicate the current pain relief strategies using opiate-based analgesia cannot achieve patient satisfaction. Liposomal bupivacaine is liposome-encapsulated bupivacaine which has been reported to be effective for up to 72 h. The study of Peri-Articular Anaesthetic for Replacement of the Knee (SPAARK) trial has been designed to assess the effectiveness of peri-articular liposomal bupivacaine and bupivacaine hydrochloride compared with peri-articular bupivacaine hydrochloride alone in the management of post-operative pain following knee replacement.

METHODS/DESIGN: The SPAARK trial is a multi-centre, patient-blinded, randomised controlled trial. The co-primary outcomes are post-operative recovery assessed by global QoR-40 scores at 72 h and cumulative pain VAS score from 6 to 72 h following surgery. Longer-term measures of the co-primary outcomes are collected at 6 weeks and 6 and 12 months post randomisation, together with secondary outcomes, i.e. the Oxford Knee Score, and the American Knee Society Score. Cumulative opiate use and fitness for discharge are measured up to 72 h post-surgery. The analysis approaches for the primary and secondary outcomes are described here, as are the descriptive statistics which will be reported. The full SPAARK protocol has already been published.

RESULTS: The co-primary outcomes will be analysed using multivariate linear regression adjusting for stratification factors and other important prognostic variables, including baseline scores in the case of the QoR-40. The adjusted mean difference between the two groups together with 97.5% confidence intervals will be reported for each of the primary outcomes. Other continuous variables will be assessed using the same method. Binary outcomes will be assessed using chi-squared tests.

DISCUSSION: The paper provides details of the planned statistical analyses for the SPAARK trial and aims to reduce the risk of outcome reporting bias from prior data knowledge. Any changes or deviations from this statistical analysis plan will be described and justified in the final study report.

TRIAL REGISTRATION: ISRCTN54191675 . Registered on 13 November 2017.

PMID:34001205 | DOI:10.1186/s13063-021-05293-7

J Ethnobiol Ethnomed. 2021 May 17;17(1):34. doi: 10.1186/s13002-021-00461-0.

ABSTRACT

BACKGROUND: The study of cultural transmission can help identify processes that influence knowledge systems dynamics and evolution, especially during childhood and youth, which are fundamental phases in acquiring survival skills. In this sense, we use the knowledge about useful restinga plants (Brazilian coastal vegetation) as an analytical model to describe, compare, and analyze cultural transmission during youth, while factoring in origin, in the Cabo Frio region, southeastern Brazil. We tested (1) whether transmission of knowledge is conservative, (2) whether immigration events define the transmission modes, (3) whether teaching is the most important social transmission cognitive process, and (4) which type of stimulus/context is most important for the knowledge transmission process.

METHODS: Questionnaires and free listings were applied to 150 high school students aged between 15 and 20 to obtain information about socioeconomic characteristics, useful plant knowledge, and cultural transmission. We analyzed the distribution of knowledge according to the informant’s origin and evaluated the models, processes, and context with which this information was transmitted. The chi-square test was used to determine the association between origin, plant knowledge, and transmission as well as to reveal the most important models, modes, and processes during youth.

RESULTS: Informants provided 299 plant citations ([Formula: see text] = 1.75; s = 1.73) related to 37 species. The categories of the most cited uses were edible (93) and medicinal (32). Statistical results showed that origin did not influence knowledge distribution and transmission. In addition, although the most relevant mode was the conservative (vertical) one, the one-to-many diffuse mode (teacher) was highlighted. The new environmental context for immigrants did not influence transmission, the main transmission process was teaching, and the learning contexts were predominantly school-related.

CONCLUSION: Plant knowledge in youth was related to local edible and medicinal plants, indicating adaptive knowledge linked to material demands for survival. While the initial models for cultural transmission are family (vertical), during the development phase of juveniles, other actors become models (one-to-many). In addition, the nature of the information (survival demand) and age are more relevant to cultural transmission than the socio-environmental context.

PMID:34001189 | DOI:10.1186/s13002-021-00461-0

Ital J Pediatr. 2021 May 17;47(1):114. doi: 10.1186/s13052-021-01064-x.

ABSTRACT

BACKGROUND: Trachoma is an infectious disease of the eye caused by Chlamydia trachomatis and transmitted via contact with eye discharge from infected persons and leading to blindness worldwide. Children less than 9 years of age affected more seriously. The disease is common where access to water and sanitation are limited.

OBJECTIVE: To determine the prevalence of active trachoma and associated factors among children aged 1-9 years in rural communities of Metema District, West Gondar Zone, Northwest Ethiopia.

METHOD: A community based cross-sectional study design was used to collect data from 792 children aged 1-9 years old in Metema district from April to May 2018. Multistage sampling technique was used to select the study participants. Pretested interviewer-administered structured questionnaire and eye examination using binocular loupe to differentiate trachoma cases was the data collection methods and tools. The bivariable and multivariable binary logistic regression model was employed for analysis. P-value < 0.05 was considered to declare statistical significance.

RESULTS: A total of 752 children aged l-9 years were enrolled in this study with response rate of 94.9%. The overall prevalence of active trachoma among the study participants was 11.8% (95% CI, 9.5-13.9). Unprotected source of water (AOR = 4.7; 95% CI: 2.5-8.9), lower household water consumption (AOR = 2.8; 95% CI: 1.3-6.0), improper latrine utilization (AOR = 3.2; 95% CI: 1.5-6.7), and frequency of face washing once per day (AOR = 5.3; 95% CI: 1.2-26.6) were the factors significantly associated with active trachoma.

CONCLUSION: The current study revealed a lower overall prevalence of active trachoma (11.8%) than the WHO threshold prevalence (20%) used to declare it as a severe public health problem. All residents and health professional should collaborate on trachoma prevention by implementing the WHO SAFE strategy- surgery for trichiasis, antibiotics, facial cleanliness and environmental improvement for further trachoma elimination.

PMID:34001198 | DOI:10.1186/s13052-021-01064-x

Zhonghua Wei Chang Wai Ke Za Zhi. 2021 May 25;24(5):403-412. doi: 10.3760/cma.j.cn.441530-20200111-00014.

ABSTRACT

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.

PMID:34000769 | DOI:10.3760/cma.j.cn.441530-20200111-00014