Tag: statistics

Front Biosci (Landmark Ed). 2023 Feb 16;28(2):29. doi: 10.31083/j.fbl2802029.

ABSTRACT

BACKGROUND: The Apoptotic protease activating factor 1 (Apaf-1) protein, as one of the factors involved in the activation of the mitochondrial apoptotic pathway, plays an important role in cancer biology. Apaf-1 expression in tumour cells has been shown to be downregulated, with significant implications for tumour progression. Hence, we investigated the expression of Apaf-1 protein in the Polish population of patients with colon adenocarcinoma without any therapy prior to radical surgery. Moreover, we assessed the relation between Apaf-1 protein expression and the clinicopathological factors. The prognostic activity of this protein was analyzed in relation to 5-year survival of patients. In order to show the localization of Apaf-1 protein at the cellular level, the immunogold labelling method was used.

METHODS: The study was conducted using the colon tissue material from patients with histopathologically confirmed colon adenocarcinoma. Immunohistochemical expression of Apaf-1 protein was performed using Apaf-1 antibody at dilution 1:600. The associations between the immunohistochemistry (IHC) expression of Apaf-1 and clinical parameters were analyzed using the Chi2 test and Chi2Yatesa test. Kaplan-Meier analysis and the log-rank test were used to verify the relationship between the intensity of Apaf-1 expression and 5-year survival rate of patients. The results were considered statistically significant when p < 0.05.

RESULTS: Apaf-1 expression was evaluated by immunohistochemical staining in whole tissue sections. Thirty-nine (33.23%) samples had strong Apaf-1 protein expression and 82 (67.77%) samples were characterized by low expression. The high expression of Apaf-1 was clearly correlated with the histological grade of the tumour (p = 0.001), proliferating cell nuclear antigen (PCNA) immunohistochemical expression (p = 0.005), age (p = 0.015), depth of invasion (p < 0.001) and angioinvasion (p < 0.001). The 5-year survival rate was significantly higher in the group of patients with high expression of this protein (log-rank, p < 0.001).

CONCLUSIONS: We can conclude that Apaf-1 expression is positively correlated with reduced survival of colon adenocarcinoma patients.

PMID:36866552 | DOI:10.31083/j.fbl2802029

J Phycol. 2023 Mar 3. doi: 10.1111/jpy.13326. Online ahead of print.

ABSTRACT

Viet Nam has a coastline of 3,200 km with thousands of islands providing diverse habitats for benthic harmful algal species including species of Gambierdiscus. Some of these species produce ciguatera toxins, which may accumulate in large carnivore fish potentially posing major threats to public health. This study reports five species of Gambierdiscus from Vietnamese waters, notably G. australes, G. caribaeus, G. carpenteri, G. pacificus, and G. vietnamensis sp. nov. All species are identified morphologically by LM and SEM, and identifications are supported by molecular analyses of nuclear rDNA (D1-D3 and D8-D10 domains of LSU, SSU, and ITS1-5.8S-ITS2 region) based on cultured material collected during 2010-2021. Statistical analyses of morphometric measurements may be used to differentiate some species if a sufficiently large number of cells are examined. Gambierdiscus vietnamensis sp. nov. is morphologically similar to other strongly reticulated species, such as G. belizeanus and possibly G. pacificus; the latter species is morphologically indistinguishable from G. vietnamensis sp. nov., but they are genetically distinct, and molecular analysis is deemed necessary for proper identification of the new species. This study also revealed that strains denoted G. pacificus from Hainan Island (China) should be included in G. vietnamensis sp. nov.

PMID:36866508 | DOI:10.1111/jpy.13326

Cytometry A. 2023 Mar 3. doi: 10.1002/cyto.a.24728. Online ahead of print.

ABSTRACT

Förster resonance energy transfer (FRET) is a radiationless interaction between a donor and an acceptor whose distance dependence makes it a sensitive tool for studying the oligomerization and the structure of proteins. When FRET is determined by measuring the sensitized emission of the acceptor, a parameter characterizing the ratio of detection efficiencies of an excited acceptor vs. an excited donor is invariably involved in the formalism. For FRET measurements involving fluorescent antibodies or other external labels, this parameter, designated by α, is usually determined by comparing the intensity of a known number of donors and acceptors in two independent samples leading to a large statistical variability if the sample size is small. Here, we present a method that improves precision by applying microbeads with a calibrated number of antibody binding sites and a donor-acceptor mixture in which donors and acceptors are present in a certain, experimentally determined ratio. A formalism is developed for determining α and the superior reproducibility of the proposed method compared to the conventional approach is demonstrated. Since the novel methodology does not require sophisticated calibration samples or special instrumentation, it can be widely applied for the quantification of FRET experiments in biological research.

PMID:36866503 | DOI:10.1002/cyto.a.24728

Gerontologist. 2023 Mar 2:gnad021. doi: 10.1093/geront/gnad021. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: The Veterans RAND 12-Item Health Survey (VR-12) is a generic patient-reported outcome measure of physical and mental health status. An adapted version of the VR-12 was developed for use with older adults living in long-term residential care (LTRC) homes in Canada: VR-12 (LTRC-C). This study aimed to evaluate the psychometric validity of the VR-12 (LTRC-C).

RESEARCH DESIGN AND METHODS: Data for this validation study were collected via in-person interviews for a province-wide survey of adults living in LTRC homes across British Columbia (N = 8,657). Three analyses were conducted to evaluate validity and reliability: 1) confirmatory factor analyses (CFA) were conducted to validate the measurement structure, 2) correlations with measures of depression, social engagement and daily activities were examined to evaluate convergent and discriminant validity and 3) Cronbach’s alpha (r) statistics were obtained to evaluate internal consistency reliability.

RESULTS: A measurement model with two correlated latent factors (representing physical health and mental health), four cross-loadings, and four correlated items resulted in acceptable fit (Root Mean Square Error of Approximation = .07; Comparative Fit Index = .98). Physical and mental health were correlated in expected directions with measures of depression, social engagement, and daily activities, though magnitudes of the correlations were quite small. Internal consistency reliability was acceptable for physical and mental health (r >0.70).

DISCUSSION AND IMPLICATIONS: This study supports the use of the VR-12 (LTRC-C) to measure perceived physical and mental health among older adults living in LTRC homes.

PMID:36866495 | DOI:10.1093/geront/gnad021

Lancet Glob Health. 2023 Mar;11 Suppl 1:S5. doi: 10.1016/S2214-109X(23)00090-6.

ABSTRACT

BACKGROUND: A high prevalence of excess weight in children younger than 5 years suggests the involvement of early-life risk factors. The preconception and pregnancy periods are crucial stages for the implementation of interventions to prevent childhood obesity. Most studies so far have evaluated the effects of early-life factors separately, with only a few investigating the combined effect of parental lifestyle factors. Our objective was to fill the literature gap regarding parental lifestyle factors in the preconception and pregnancy periods and to study their association with the risk of overweight in children after the age of 5 years.

METHODS: We harmonised and interpreted data from four European mother-offspring cohorts (EDEN [comprising 1900 families], Elfe [comprising 18 000 families], Lifeways [comprising 1100 families], and Generation R [comprising 9500 families]). Written informed consent was obtained from parents of all involved children. Lifestyle factor data collected through questionnaires comprised parental smoking, BMI, gestational weight gain, diet, physical activity, and sedentary behaviour. We applied principal component analyses to identify multiple lifestyle patterns in preconception and pregnancy. Their association with child BMI z-score and risk of overweight (including obesity, overweight and obesity, as defined by the International Task Force reference) between the ages of 5 and 12 years were assessed using cohort-specific multivariable linear and logistic regression models (adjusted for confounders including parental age, education level, employment status, geographic origin, parity, and household income).

FINDINGS: Among the various lifestyle patterns identified in all cohorts, the two that better explained variance were high parental smoking plus low maternal diet quality or high maternal sedentary behaviour, and high parental BMI plus low gestational weight gain. Overall, we observed that patterns characterised by high parental BMI, smoking, low-quality diet, or sedentary lifestyle before or during pregnancy were associated with higher BMI z-scores and risk of overweight and obesity in children aged 5-12 years.

INTERPRETATION: Our data contribute to a better understanding of how parental lifestyle factors might be associated with the risk of childhood obesity. These findings are valuable to inform future family-based and multi-behavioural child obesity prevention strategies in early life.

FUNDING: European Union’s Horizon 2020 under the ERA-NET Cofund action (reference 727565) and European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, EndObesity).

PMID:36866482 | DOI:10.1016/S2214-109X(23)00090-6

Lancet Glob Health. 2023 Mar;11 Suppl 1:S16. doi: 10.1016/S2214-109X(23)00099-2.

ABSTRACT

BACKGROUND: 70% of children with obesity and overweight live in low-income and middle-income countries. Several interventions have been done to reduce the prevalence of childhood obesity and prevent incident cases. Hence, we did a systematic review and meta-analysis to determine the effectiveness of these interventions in reducing and preventing childhood obesity.

METHODS: We conducted a search for randomised controlled trials and quantitative non-randomised studies published on MEDLINE, Embase, Web of Science, and PsycINFO databases between Jan 1, 2010, and Nov 1, 2022. We included interventional studies on the prevention and control of obesity in children up to age 12 years in low-income and middle-income countries. Quality appraisal was performed using Cochrane’s risk-of-bias tools. We did three-level random-effects meta-analyses and explored the heterogeneity of studies included. We excluded critical risk-of-bias studies from primary analyses. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation.

FINDINGS: The search generated 12 104 studies, of which eight studies were included involving 5734 children. Six studies were based on obesity prevention, most of which targeted behavioural changes with a focus on counselling and diet, and a significant reduction in BMI was observed (standardised mean difference 2·04 [95% CI 1·01-3·08]; p<0·001). In contrast, only two studies focused on the control of childhood obesity; the overall effect of the interventions in these studies was not significant (p=0·38). The combined studies of prevention and control had a significant overall effect, with study-specific estimates ranging between 0·23 and 3·10, albeit with a high statistical heterogeneity (I²>75%).

INTERPRETATION: Preventive interventions, such as behavioural change and diet modification, are more effective than control interventions in reducing and preventing childhood obesity.

FUNDING: None.

PMID:36866473 | DOI:10.1016/S2214-109X(23)00099-2

Lancet Glob Health. 2023 Mar;11 Suppl 1:S1. doi: 10.1016/S2214-109X(23)00086-4.

ABSTRACT

BACKGROUND: Five novel subtypes of adult-onset diabetes were identified in 2018. We aimed to investigate whether childhood adiposity increases the risks of these subtypes using a Mendelian randomisation design, and to explore genetic overlaps between body size (self-reported perceived body size [ie, thinner, about average, or plumper] in childhood, and BMI measured in adulthood) and these subtypes.

METHODS: The Mendelian randomisation and genetic correlation analyses were based on summary statistics from European genome-wide association studies of childhood body size (n=453 169), adult BMI (n=359 983), latent autoimmune diabetes in adults (n=8581), severe insulin-deficient diabetes (n=3937), severe insulin-resistant diabetes (n=3874), mild obesity-related diabetes (n=4118), and mild age-related diabetes (n=5605). We identified 267 independent genetic variants as instrumental variables for childhood body size in the Mendelian randomisation analysis of latent autoimmune diabetes in adults and 258 independent genetic variants as instrumental variables for other diabetes subtypes. The inverse variance-weighted method was used as the primary estimator in the Mendelian randomisation analysis, supplemented by other Mendelian randomisation estimators. We calculated overall genetic correlations (rg) between childhood or adult adiposity and different subtypes using linkage disequilibrium score regression.

FINDINGS: A large childhood body size was associated with increased risk of latent autoimmune diabetes in adults (odds ratio [OR] 1·62, 95% CI 1·95-2·52), severe insulin-deficient diabetes (OR 2·45, 1·35-4·46), severe insulin-resistant diabetes (OR 3·08, 1·73-5·50), and mild obesity-related diabetes (OR 7·70, 4·32-13·7), but not mild age-related diabetes in the main Mendelian randomisation analysis. Other Mendelian randomisation estimators gave similar results and did not support the existence of horizontal pleiotropy. There was genetic overlap between childhood body size and mild obesity-related diabetes (rg 0·282; p=0·0003), and between adult BMI and all diabetes subtypes.

INTERPRETATION: This study provides genetic evidence that higher childhood adiposity is a risk factor for all subtypes of adult-onset diabetes, except mild age-related diabetes. It is therefore important to prevent and intervene in childhood overweight or obesity. There is shared genetic contribution to childhood obesity and mild obesity-related diabetes.

FUNDING: The study was supported by the China Scholarship Council, the Swedish Research Council (grant number 2018-03035), Research Council for Health, Working Life and Welfare (grant number 2018-00337), and Novo Nordisk Foundation (grant number NNF19OC0057274).

PMID:36866468 | DOI:10.1016/S2214-109X(23)00086-4

Oncologist. 2023 Mar 2:oyad025. doi: 10.1093/oncolo/oyad025. Online ahead of print.

ABSTRACT

BACKGROUND: In 2020, pembrolizumab was approved as a therapy for triple-negative breast cancer (TNBC) with the companion diagnostic DAKO 22C3 programmed death ligand-1 (PD-L1) immunohistochemistry assay. The study aimed to determine the landscape of PD-L1 expression as detected by the DAKO 22C3 PD-L1 assay in breast cancer subtypes and compare the clinicopathologic and genomic characteristics of PD-L1 positive and negative TNBC.

METHODS: PD-L1 expression using the DAKO 22C3 antibody was scored using a combined positive score (CPS) and positive status was defined as CPS ≥10. Comprehensive genomic profiling was performed using the FoundationOne CDx assay.

RESULTS: Of the 396 BC patients stained with DAKO 22C3, the majority were HR+/HER2- and TNBC (42% and 36%, respectively). Median PD-L1 expression and frequency of CPS ≥10 was highest in TNBC cases (median: 7.5, 50% CPS ≥10) and lowest in the HR+/HER2- group (median: 1.0, 15.5% CPS ≥10) (P < .0001). A comparison of PD-L1 positive and PD-L1 negative TNBC demonstrated no significant differences in clinicopathologic or genomic characteristics. TNBC tissue samples from the breast did have an observed enrichment for PD-L1 positivity compared to TNBC tissue samples from a metastatic site (57% vs. 44%), but this was not statistically significant (P = .1766). In the HR+/HER2- group, genomic alterations in TP53, CREBBP, and CCNE1 were more prevalent and genomic loss of heterozygosity was higher in the PD-L1(+) group compared to the PD-L1(-) group.

CONCLUSIONS: The subtypes of breast cancer have distinct patterns of PD-L1 expression, supporting that further research of immunotherapies may include specific evaluation of optimum cutoffs for non-TNBC patients. In TNBC, PD-L1 positivity is not associated with other clinicopathologic or genomic features and should be integrated into future studies of immunotherapy efficacy.

PMID:36866462 | DOI:10.1093/oncolo/oyad025

Perm J. 2023 Mar 3:1-9. doi: 10.7812/TPP/22.145. Online ahead of print.

ABSTRACT

Introduction Alcohol screening and brief intervention has been shown to reduce unhealthy alcohol use, although widespread adoption into primary care practice has been slow. Patients undergoing bariatric surgery are at an increased risk of unhealthy alcohol use. The authors compared a novel, web-based screening tool called ATTAIN to usual care for real-world effectiveness and accuracy among bariatric surgery registry patients. Methods The authors analyzed the results of a quality improvement project that tested ATTAIN among bariatric surgery registry patients. Participants were stratified into 3 groups by surgery status (preoperative vs postoperative) and prior screening for unhealthy alcohol use (screened vs not screened in the past year). Participants in these 3 groups were divided into intervention plus usual care (n = 2249) and control (n = 2130) groups, with intervention being an email to complete ATTAIN, and control being usual care (eg, office-based screening). Primary outcomes included screening and positivity rates for unhealthy drinking behavior between groups. Secondary outcomes included positivity rates via ATTAIN vs usual care for individuals who were screened by both modalities. Chi-square test was used for statistical analysis. Results The overall screening rates were 67.4% (intervention arm) and 38.6% (control). The ATTAIN response rate was 47% of those invited. The overall positive screen rate was 7.7% (intervention) and 2.6% (control); p < .001 for both. For dual screened intervention participants, the positive screen rate was 10% (ATTAIN) vs 2% (usual care) with p < .001. Conclusion ATTAIN is a promising method of increasing screening and detection rates for unhealthy drinking behavior.

PMID:36866440 | DOI:10.7812/TPP/22.145

HERD. 2023 Mar 2:19375867231159130. doi: 10.1177/19375867231159130. Online ahead of print.

ABSTRACT

AIM: To examine how the spatial topology of the operating room (OR) within the medical center impacts surgical team communication.

BACKGROUND: Understanding the complex association between surgical team communication and the OR’s spatial network location is critical to patient safety. Effective surgical communication is associated with fewer adverse events and medical errors.

METHODS: We employed a cross-sectional, quantitative, case study, and network-centric study design. We studied the population of 204 clinicians in a large military medical center (36 perioperative nurses, 34 surgical technicians, 62 anesthesia providers, and 72 surgeons), focusing on surgical teams with cases completed within duty hours. Data were collected from December 2020 to June 2021 using an electronic survey. Spatial network analysis was done using electronic floor plans. Statistical analysis was done with descriptive statistics and linear regressions. The outcomes were general and task-specific communication, and team-level variables were aggregated from scores for all team members. Spatial effects were assessed with network centrality (degree, Laplacian, and betweenness).

RESULTS: The individual-level survey response rate was 77% (157 of 204). Data were collected on 137 surgical teams. On a 5-point scale, general and task-specific communication ranged from 3.4 to 5.0 and 3.5 to 5.0, respectively (for both, median = 4.7). Team size ranged from 4 to 6 individuals (median = 4). Surgical suites with higher network centralities were associated with significantly lower communication scores.

CONCLUSIONS: The OR’s spatial network location has important impacts on surgical team communication. Our findings have design and workflow implications for ORs and even surgical care in combat zones.

PMID:36866407 | DOI:10.1177/19375867231159130