Category: Statistics

Syst Biol. 2024 Nov 7:syae064. doi: 10.1093/sysbio/syae064. Online ahead of print.

ABSTRACT

Biology has become a highly mathematical discipline in which probabilistic models play a central role. As a result, research in the biological sciences is now dependent on computational tools capable of carrying out complex analyses. These tools must be validated before they can be used, but what is understood as validation varies widely among methodological contributions. This may be a consequence of the still embryonic stage of the literature on statistical software validation for computational biology. Our manuscript aims to advance this literature. Here, we describe, illustrate and introduce new good practices for assessing the correctness of a model implementation, with an emphasis on Bayesian methods. We also introduce a suite of functionalities for automating validation protocols. It is our hope that the guidelines presented here help sharpen the focus of discussions on (as well as elevate) expected standards of statistical software for biology.

PMID:39506375 | DOI:10.1093/sysbio/syae064

Bioanalysis. 2024 Nov 6:1-6. doi: 10.1080/17576180.2024.2418284. Online ahead of print.

ABSTRACT

The ICH M10 guideline establishes global standards for bioanalytical method validation for pharmacokinetic assays, focusing on data reliability and accuracy across studies. A significant component is cross-validation, which should be performed to ensure data comparability when multiple methods or laboratories are involved in a single study or across studies where comparison will be performed. However, ICH M10 does not specify acceptance criteria for cross-validation, creating challenges for the industry because traditionally many laboratories have always utilized acceptance criteria to “pass” or “fail” the study. This editorial discusses how bioanalytical labs should conduct cross-validation for PK assays post-ICH M10, highlighting the role of statistical methods and the need for close collaboration with clinical pharmacology and biostatistics departments. Proper implementation and strategic focus on relevant studies are essential for effective cross-validation.

PMID:39506370 | DOI:10.1080/17576180.2024.2418284

Biophys J. 2024 Nov 5:S0006-3495(24)00712-4. doi: 10.1016/j.bpj.2024.11.003. Online ahead of print.

ABSTRACT

All living cells vibrate depending on metabolism. It has been hypothesized that vibrations are unique for a given phenotype and thereby suitable to diagnose cancer type, stage, and pre-assess the effectiveness of pharmaceutical treatments in real time. However, cells exhibit highly variable vibrational signals, can be subject to environmental noise, and may be challenging to differentiate, having so far limited the phenomenon’s applicability. Here, we combined the sensitive method of force-spectroscopy using optical tweezers (OT) with comprehensive statistical analysis. After data acquisition, the signal was decomposed into its spectral components via Fast Fourier Transform (FFT). Peaks were parameterized and subjected to Principal Component Analysis (PCA), to perform an unbiased multivariate statistical evaluation. This method, which we term Cell Vibrational Profiling (CVP), systematically assesses cellular vibrations. To validate CVP technique, we conducted experiments on five U251 glioblastoma (GBM) cells, using 8-10 μm polystyrene beads as a control for comparison. We collected raw data using OT, segmenting into 150+ five-second intervals. Each segment was converted into power spectra (PS) representing a frequency resolution of 10,000 Hz for both cells and controls. U251 GBM cells exhibited significant vibrations at 402.6, 1254.6, 1909.0, 2169.4, and 3462.8 Hz (p<0.0001). This method was further verified with PCA modelling, which revealed that in cell-cell comparisons using the selected frequencies, overlap frequently occurred, and clustering was difficult to discern. In contrast, comparison between cell-bead models showed that clustering was easily distinguishable. Our paper establishes CVP as an unbiased, comprehensive technique to analyze cell vibrations. This technique effectively differentiates between cell types and evaluates cellular responses to therapeutic interventions. Notably, CVP is a versatile, cell-agnostic technique requiring minimal sample preparation and no labelling or external interference. By enabling definitive phenotypic assessments, CVP holds promise as a diagnostic tool and could significantly enhance the evaluation of pharmaceutical treatments.

PMID:39506334 | DOI:10.1016/j.bpj.2024.11.003

Br J Nutr. 2024 Nov 7:1-6. doi: 10.1017/S0007114524001363. Online ahead of print.

ABSTRACT

A well-functioning immune system requires balanced immune responses. In vitro studies have shown that plant stanols contribute to restoring the T-helper (Th)1/Th2 ratio when it is imbalanced. However, effects of plant stanols on healthy immune responses are unknown. Therefore, we studied effects of recommended (2·5 g/d) or high (9·0 g/d) plant stanol intakes on the Th1/Th2 cytokine balance in immunologically healthy subjects. In two RCTs, peripheral blood mononuclear cells (PBMCs) were isolated, cultured, and stimulated with 5 µg/ml Phytohemagglutinin-M to study ex vivo cytokine production. In the first study, twenty participants consumed margarines (2·5 g/d plant stanols) or control for three weeks. In the second study, nineteen participants consumed margarines and yogurts (9·0 g/d plant stanols) or control for four weeks. T-cell cytokine concentrations were measured in culture medium and in study 2 a standardized Th1/Th2 index was calculated. Serum lipids and non-cholesterol sterols were also measured. Compliance was confirmed by significant increases in serum total cholesterol (TC)-standardized sitostanol and campestanol levels in both studies. Changes in ex vivo cytokine production and Th1/Th2 index did not differ between intervention and control groups. In the first study, no statistically significant changes were observed in lipid and lipoprotein concentrations. In the second study, LDL cholesterol significantly decreased compared to control (-0·77 (-1·11, -0·42) mmol/l; P < 0·001). Recommended (2·5 g/d) or high (9·0 g/d) intakes of plant stanols did not alter PBMC ex vivo cytokine production in immunologically healthy subjects. This suggests that plant stanols might only affect immune function when Th1/Th2 immune responses are imbalanced.

PMID:39506323 | DOI:10.1017/S0007114524001363

Nutr Health. 2024 Nov 6:2601060241289975. doi: 10.1177/02601060241289975. Online ahead of print.

ABSTRACT

STUDY PURPOSE: This study aims to critically evaluate ChatGPT’s impact on cybersecurity in healthcare and education sectors.

METHODS: This study employed a cross-sectional survey design, collecting data from healthcare and educational professionals in Saudi Arabia through a structured questionnaire, with 205 healthcare workers’ and 214 educators. The survey assessed perceptions of ChatGPT’s impact on cybersecurity opportunities and challenges, with data analyzed using descriptive statistics and ANOVA to explore differences across professional roles.

RESULTS: Healthcare professionals viewed artificial intelligence (AI) more favorably (mean scores 4.24 and 4.14) than those in education, who showed moderate enthusiasm (mean scores 2.55 to 3.54). Concerns over data privacy and the cost of securing AI were significant, with high mean scores of 3.59 indicating widespread apprehension.

CONCLUSION: A balanced approach to ChatGPT’s integration that carefully considers ethical implications, data privacy, and the technology’s dual-use potential is required.

PMID:39506281 | DOI:10.1177/02601060241289975

Cardiol Young. 2024 Nov 7:1-5. doi: 10.1017/S1047951124035959. Online ahead of print.

ABSTRACT

BACKGROUND: Endomyocardial biopsy remains the gold standard for cardiac cellular rejection surveillance after heart transplantation. We studied a novel non-invasive index of left ventricular relaxation to detect cardiac cellular rejection in paediatric heart transplant patients.

METHODS: This is a single-centre retrospective study of paediatric heart transplant patients who underwent endomyocardial biopsy from June 2014 to September 2021. Left ventricular relaxation index was calculated as the sum of diastolic tissue Doppler imaging velocities (E) of the left ventricular lateral, septal, and posterior walls divided by the percentage of the left ventricular posterior wall thinning by M-mode. Statistical analysis included t-tests and Mann-Whitney tests to compare means and medians between treatment and non-treatment groups. We used the cut-off with the maximum Youden index to compare the sensitivity and specificity of left ventricular relaxation index to detect rejection.

RESULTS: The study included 65 patients who underwent 246 cardiac catheterizations and endomyocardial biopsies. Out of 246, 192 procedures were included and 54 were excluded due to recent transplants or lack of echocardiographic data. A total of 114 demonstrated Grade 0R, 68 Grade 1R, 8 Grade 2R, and 2 Grade 3R allograft rejection. The difference in mean left ventricular relaxation index between treatment versus non-treatment groups (2R, 3R vs. 0R, 1R) was not statistically significant (p = 0.917). A left ventricular relaxation index cut-off of 0.73 had the highest Youden index with good sensitivity (100%) and poor specificity (23%) for detecting rejections with grades 2R and 3R.

CONCLUSION: Left ventricular relaxation index, a novel index of left ventricular relaxation, was not a sensitive or specific predictor of cardiac cellular rejection in paediatric heart transplants.

PMID:39506276 | DOI:10.1017/S1047951124035959

Int J Low Extrem Wounds. 2024 Nov 6:15347346241292377. doi: 10.1177/15347346241292377. Online ahead of print.

ABSTRACT

The aim of this study was to identify and analyze the incidence rate of amputations and their risk factors in people with Diabetes Mellitus (DM) in two specialized outpatient clinics in Brazil. This is an epidemiological, retrospective cohort study using data collected from electronic health records of 281 adult diabetic patient types 1 or 2; attended in specialized outpatient service between 2015 and 2020. Statistical analyses were performed using the 2 sample t-test or Wilcoxon-Mann-Whitney test, for quantitative variables, and the Pearson’s χ2 test or Fisher’s exact test for categorical variables. The investigation of the risk factors for amputation was carried out through logistic regression. The study was approved by ethical committee. The sample mean age was 65.6 years (SD 13.05), predominating male gender n = 211 (75%), type 2 DM n = 223 (86.7%), with cardiovascular disease n = 143 (63.2%), and about 68.7% (n = 156) with peripheral arterial disease (PAD). Seventy-seven had lower limb amputation (LLA), with a rate incidence of 31.9% during five years. Logistic regression analysis showed the following associations with amputation: Diabetic peripheral neuropathy increased the rate of amputation by 3.6 times (OR = 3.631, 95% CI = 1.214-11.353; P = .022), and peripheral arterial disease increased by 10 times (OR = 10.631; 95% CI = 2.969-57.029; P = .001). The LLA in individuals with DM in two specialized outpatient services was higher compared to international literature; DPN and PAD were confirmed as risk factors for amputation, according to literature. This finding suggests that the study population faces an increased risk of amputation, highlighting the urgent need for targeted interventions and implementing robust preventive strategies to transform the current scenario and mitigate these severe outcomes. A comprehensive approach is essential to proactively address the underlying issues and reduce the prevalence and impact of amputations in Brazil.

PMID:39506269 | DOI:10.1177/15347346241292377

Geriatr Gerontol Int. 2024 Nov 6. doi: 10.1111/ggi.15007. Online ahead of print.

ABSTRACT

AIM: To estimate the prevalence of nocturia in middle-aged and elderly men and evaluate its associated factors and changes over time.

METHODS: Data of middle-aged and older men aged ≥40 years from the 2007-2008 and 2017-2020 cycles of the National Health and Nutrition Examination Survey were retrospectively analyzed. The prevalence of nocturia was estimated using participant questionnaires on nocturia, lifestyle-related factors, and health factors, and its decadal changes were examined using multivariate logistic regression analysis to determine related factors associated with the prevalence of nocturia.

RESULTS: The prevalence of nocturia was 38.0% in 2007-2008 and 39.6% in 2017-2020, with no significant increase observed (P = 0.3989). Being a non-Hispanic black was positively correlated with nocturia (adjusted odds ratio [AOR] = 1.54, 1.22-1.93, P < 0.001), whereas the correlation with being a Mexican American disappeared (AOR = 1.25, 0.90-1.73, P = 0.187). Diabetes (AOR = 1.32, 1.07-1.64, P = 0.010) and sleep disorders (AOR = 1.31, 1.07-1.60, P = 0.008) showed a statistically significant positive correlation with nocturia, whereas a significant negative correlation was observed between employment (AOR = 0.66, 0.54-0.82, P < 0.001) and nocturia. Above-high-school education (AOR = 0.60, 0.47-0.76, P < 0.001) showed a constant trend toward a negative correlation with nocturia. The correlation between high school education or general educational development and nocturia disappeared (AOR = 0.81, 0.62-1.05, P = 0.112).

CONCLUSION: Diabetes and sleep disorders contribute to the development of nocturia, while work and high educational attainment can actively combat nocturia. Geriatr Gerontol Int 2024; ••: ••-••.

PMID:39506265 | DOI:10.1111/ggi.15007

Health Psychol Rev. 2024 Nov 6:1-10. doi: 10.1080/17437199.2024.2425689. Online ahead of print.

ABSTRACT

How often do we reflect on the potential moral or value implications – what is right, wrong, has value and is (in)appropriate – of seemingly trivial analytical decisions, such as how to dichotomise a variable? I argue that analytical choices relate to multifaceted and oftentimes challenging moral issues that scientists should take into deeper consideration. Here, I illustrate a variety of potential considerations about moral values, including issues like exclusion, marginalisation, autonomy, responsibility, non-maleficence in relation to various common analytical choices and practices, such as the use of thresholds for disease diagnosis or population definition, the use of composite measures in the context of clarifying effects, classification practices, decisions on variable selection, as well as decisions relating to (dis)aggregation of data. I discuss these examples in the context of reasonable theoretical or statistical reservations. I advocate for deeper engagement with the difficult moral implications of analytical decisions, and for a principled and pluralistic science, that is also a more robust science. Such a science can include diverse moral views through a coupled ethical-epistemic approach, sensitivity tests, multiverse analysis, as well as stronger commitments to participatory and mutual learning practices.

PMID:39506261 | DOI:10.1080/17437199.2024.2425689

Br J Nurs. 2024 Nov 7;33(20):976-982. doi: 10.12968/bjon.2023.0297.

ABSTRACT

BACKGROUND: Palliative and end-of-life care (EoLC) education is available to all community and hospital healthcare staff in one NHS trust in the north-east of England. It is also available to care home and domiciliary care staff within the geographical area of the trust.

AIMS: This service evaluation assessed the effect of current in-house education on staff confidence levels in delivering palliative and EoLC. It also examined staff perceptions of how attendance at these courses impacted on the palliative and EoLC patients receive across the locality.

METHOD: A mixed-methods approach was undertaken. Anonymous data were collected via surveys (n=238) sent out in March 2023 covering educational courses that were delivered from 1 January to 31 December 2022 with a 13% response rate. Quantitative data were analysed using descriptive statistics. Qualitative data were explored using Braun and Clarke’s (2012) six-stage approach to thematic analysis. A second staff member was asked to review the data to increase the trustworthiness of the study.

FINDINGS: Staff confidence levels in delivering palliative and EoLC increased by 19% (somewhat confident) and 23% (extremely confident) following attendance at trust education. Staff perceived that those patients received better palliative and EoLC as a result their attendance at these courses. The qualitative data identified five main themes: symptom control, psychological support, holistic care, patient advocacy, and advance care planning. Limitations of the study included the low survey response rate and lack of exploration of patient/carer perceptions directly.

CONCLUSION: Palliative and EoLC education can increase staff confidence levels in care delivery and, as perceived by staff, results in better care for patients receiving palliative and EoLC. These findings provide evidence for the trust to consider making palliative and EoLC training mandatory, which could also be considered more widely regionally and nationally.

PMID:39506220 | DOI:10.12968/bjon.2023.0297