Category: Statistics

J Appl Genet. 2023 Oct 25. doi: 10.1007/s13353-023-00795-3. Online ahead of print.

ABSTRACT

Knowledge of the magnitude of gene effects and their interactions, their nature, and contribution to determining quantitative traits is very important in conducting an effective breeding program. In traditional breeding, information on the parameter related to additive gene effect and additive-additive interaction (epistasis) and higher-order additive interactions would be useful. Although commonly overlooked in studies, higher-order interactions have a significant impact on phenotypic traits. Failure to account for the effect of triplet interactions in quantitative genetics can significantly underestimate additive QTL effects. Understanding the genetic architecture of quantitative traits is a major challenge in the post-genomic era, especially for quantitative trait locus (QTL) effects, QTL-QTL interactions, and QTL-QTL-QTL interactions. This paper proposes using weighted multiple linear regression to estimate the effects of triple interaction (additive-additive-additive) quantitative trait loci (QTL-QTL-QTL). The material for the study consisted of 126 doubled haploid lines of winter wheat (Mandub × Begra cross). The lines were analyzed for 18 traits, including percentage of necrosis leaf area, percentage of leaf area covered by pycnidia, heading data, and height. The number of genes (the number of effective factors) was lower than the number of QTLs for nine traits, higher for four traits and equal for five traits. The number of triples for unweighted regression ranged from 0 to 9, while for weighted regression, it ranged from 0 to 13. The total aaa_gu effect ranged from – 14.74 to 15.61, while aaa_gw ranged from – 23.39 to 21.65. The number of detected threes using weighted regression was higher for two traits and lower for four traits. Forty-nine statistically significant threes of the additive-by-additive-by-additive interaction effects were observed. The QTL most frequently occurring in threes was 4407404 (9 times). The use of weighted regression improved (in absolute value) the assessment of QTL-QTL-QTL interaction effects compared to the assessment based on unweighted regression. The coefficients of determination for the weighted regression model were higher, ranging from 0.8 to 15.5%, than for the unweighted regression. Based on the results, it can be concluded that the QTL-QTL-QTL triple interaction had a significant effect on the expression of quantitative traits. The use of weighted multiple linear regression proved to be a useful statistical tool for estimating additive-additive-additive (aaa) interaction effects. The weighted regression also provided results closer to phenotypic evaluations than estimator values obtained using unweighted regression, which is closer to the true values.

PMID:37878169 | DOI:10.1007/s13353-023-00795-3

J Endocrinol Invest. 2023 Oct 25. doi: 10.1007/s40618-023-02209-x. Online ahead of print.

ABSTRACT

PURPOSE: The prevalence of diabetes is increasing worldwide. The associations between the lipid profile and glycated hemoglobin (HbA1c), fasting glucose, and diabetes remain unclear, so we aimed to perform a cohort study and a two-sample Mendelian randomization (MR) study to investigate the causality between blood lipid profile and HbA1c, fasting glucose, and diabetes.

METHODS: A total of 25,171 participants from the Taiwan Biobank were enrolled. We applied a cohort study and an MR study to assess the association between blood lipid profile and HbA1c, fasting glucose, and diabetes. The summary statistics were obtained from the Asian Genetic Epidemiology Network (AGEN), and the estimates between the instrumental variables (IVs) and outcomes were calculated using the inverse-variance weighted (IVW) method. A series of sensitivity analyses were performed.

RESULTS: In the cohort study, high-density lipoprotein cholesterol (HDL-C) was negatively associated with HbA1c, fasting glucose, and diabetes, while the causal associations between HDL-C and HbA1c (β_IVW = – 0.098, p = 0.003) and diabetes (β_IVW = – 0.594, p < 0.001) were also observed. Furthermore, there was no pleiotropy effect in this study using the MR-Egger intercept test and MR-PRESSO global test.

CONCLUSIONS: Our results support the hypothesis that a genetically determined increase in HDL-C is causally related to a reduction in HbA1c and a lower risk of diabetes.

PMID:37878156 | DOI:10.1007/s40618-023-02209-x

Breast Cancer Res Treat. 2023 Oct 25. doi: 10.1007/s10549-023-07042-7. Online ahead of print.

ABSTRACT

PURPOSE: Up to 40% of the 56,000 women diagnosed with breast cancer each year in the UK undergo mastectomy. Seroma formation following surgery is common, may delay wound healing, and be uncomfortable or delay the start of adjuvant treatment. Multiple strategies to reduce seroma formation include surgical drains, flap fixation and external compression exist but evidence to support best practice is lacking. We aimed to survey UK breast surgeons to determine current practice to inform the feasibility of undertaking a future trial.

METHODS: An online survey was developed and circulated to UK breast surgeons via professional and trainee associations and social media to explore current attitudes to drain use and management of post-operative seroma. Simple descriptive statistics were used to summarise the results.

RESULTS: The majority of surgeons (82/97, 85%) reported using drains either routinely (38, 39%) or in certain circumstances (44, 45%). Other methods for reducing seroma such as flap fixation were less commonly used. Wide variation was reported in the assessment and management of post-operative seromas. Over half (47/91, 52%) of respondents felt there was some uncertainty about drain use after mastectomy and axillary surgery and two-thirds (59/91, 65%) felt that a trial evaluating the use of drains vs no drains after simple breast cancer surgery was needed.

CONCLUSIONS: There is a need for a large-scale UK-based RCT to determine if, when and in whom drains are necessary following mastectomy and axillary surgery. This work will inform the design and conduct of a future trial.

PMID:37878150 | DOI:10.1007/s10549-023-07042-7

Cell Mol Neurobiol. 2023 Oct 25. doi: 10.1007/s10571-023-01428-3. Online ahead of print.

ABSTRACT

Carpal tunnel syndrome (CTS) is one of the most common work-related musculoskeletal disorders. The present study sought to identify putative causal proteins for CTS. We conducted a two-sample Mendelian randomization (MR) analysis to evaluate the causal association between 2859 plasma proteins (N = 35,559) and CTS (N = 1,239,680) based on the published GWAS summary statistics. Then we replicated the significant associations using an independent plasma proteome GWAS (N = 10,708). Sensitivity analyses were conducted to validate the robustness of MR results. Multivariate MR and mediation analyses were conducted to evaluate the mediation effects of body mass index (BMI), type 2 diabetes (T2D), and arm tissue composition on the association between putative causal proteins and CTS. Colocalization analysis was used to examine whether the identified proteins and CTS shared causal variant(s). Finally, we evaluated druggability of the identified proteins. Ten plasma proteins were identified as putative causal markers for CTS, including sCD14, PVR, LTOR3, CTSS, SIGIRR, IFNL3, ASPN, TM11D, ASIP, and ITIH1. Sensitivity analyses and reverse MR analysis validated the robustness of their causal effects. Arm tissue composition, BMI, and T2D may play a fully/partial mediating role in the causal relationships of ASIP, TM11D, IFNL3, PVR, and LTOR3 with CTS. The association of ASPN and sCD14 with CTS were supported by colocalization analysis. Druggability assessment demonstrated that sCD14, CTSS, TM11D, and IFNL3 were potential drug therapeutic targets. The present study identified several potential plasma proteins that were causally associated with CTS risk, providing new insights into the pathogenesis of protein-mediated CTS and offering potential targets for new therapies.

PMID:37878141 | DOI:10.1007/s10571-023-01428-3

Lasers Med Sci. 2023 Oct 25;38(1):242. doi: 10.1007/s10103-023-03915-x.

ABSTRACT

The aim of this study is to assess the influence of various Er:YAG laser energies on dentin surface micromorphology and dentine-resin shear bond strength (SBS). Eighty dentin specimens were prepared and divided randomly into ten groups: control group (CG), phosphoric acid-etched group (AG), four laser-conditioned groups treated with various pulse energies of 40, 60, 80, and 100 mJ (L40, L60, L80, L100), and four laser-conditioned acid-etched groups (LA40, LA60, LA80, LA100). Two specimens from each group underwent scanning electron microscopy examination, while the remaining six were subjected to the dentin-resin SBS test. Statistical analyses included Welch’s analysis of variance (ANOVA), followed by post hoc Tamhane’s T2 multiple comparisons test, Pearson’s correlation, and Fisher’s exact test. Pulse energies of 60, 80, and 100 mJ fully exposed the dentin tubule orifices, although 100 mJ lead to microcracks. Laser-conditioned surfaces exhibited smaller tubule diameters compared to acid-etched surfaces, and tubule diameters positively correlated with dentin-resin SBS. Laser-conditioned groups showed lower SBS values, while laser-conditioned acid-etched groups demonstrated higher SBS values. No significant relationship was observed between dentin surface roughness and SBS. The range of laser energies used for dentin conditioning had limited effects on SBS or failure modes. Laser conditioning with energies ranging from 40 to 100 mJ effectively removes the smear layer from the dentin surface. However, to enhance dentin-resin bond strength, further acid etching of the laser-conditioned surface is necessary.

PMID:37878132 | DOI:10.1007/s10103-023-03915-x

Appl Psychophysiol Biofeedback. 2023 Oct 25. doi: 10.1007/s10484-023-09606-1. Online ahead of print.

ABSTRACT

Core stabilization training utilizes principles of motor learning to retrain control of the trunk muscles and lead to improvements in chronic non-specific low back pain (CNLBP). To compare the effects of biofeedback sensor and conventional physiotherapist (PT) feedback during core stabilization and activity training in patients with CNLBP. Thirty-eight patients with CNLBP were randomly assigned to Biofeedback (n = 19) or PT feedback (n = 19) groups. Patients continued 12 sessions of combined core stabilization and activity training. An auditory and tactile biofeedback was given using a validated tilt sensor integrated with an application in the Biofeedback group. An experienced PT provided verbal and tactile feedback to maintain the neutral position in the PT Feedback group. The outcomes were; disability (Revised Oswestry Disability Index-RODI), muscle activity (m.transversus abdominis and m.multifidus), pain (Visual Analog Scale-VAS), proprioception error of the trunk, patient beliefs (Fear Avoidance Beliefs Questionnaire-FABQ) and presence of depressive symptoms (Beck Depression Index-BDI), and quality of life (Short Form (SF)-36). The main effect of time were statistically significant on VAS, RODI, m.transversus abdominis and m.multifidus muscle activities, flexion, and extension proprioception error of the trunk, FABQ, BDI, and SF-36 scores in Biofeedback and PT feedback groups (p < 0.05 for all). The time X group interaction was significant on flexion and extension proprioception error of the trunk PT feedback group (consecutively; p = 0.004, p = 0.022). Biofeedback sensor or PT feedback during core stabilization training equally improves pain, disability, muscle activity, depressive symptoms, patient beliefs, and quality of life in patients with CNLBP.

PMID:37878122 | DOI:10.1007/s10484-023-09606-1

Prehosp Disaster Med. 2023 Oct 25:1-8. doi: 10.1017/S1049023X23006544. Online ahead of print.

ABSTRACT

BACKGROUND: Pediatric patients transferred by Emergency Medical Services (EMS) from urgent care (UC) and office-based physician practices to the emergency department (ED) following activation of the 9-1-1 EMS system are an under-studied population with scarce literature regarding outcomes for these children. The objectives of this study were to describe this population, explore EMS level-of-care transport decisions, and examine ED outcomes.

METHODS: This was a retrospective review of patients zero to <15 years of age transported by EMS from UC and office-based physician practices to the ED of two pediatric receiving centers from January 2017 through December 2019. Variables included reason for transfer, level of transport, EMS interventions and medications, ED medications/labs/imaging ordered in the first hour, ED procedures, ED disposition, and demographics. Data were analyzed with descriptive statistics, X test, point biserial correlation, two-sample z test, Mann-Whitney U test, and 2-way ANOVA.

RESULTS: A total of 450 EMS transports were included in this study: 382 Advanced Life Support (ALS) runs and 68 Basic Life Support (BLS) runs. The median patient age was 2.66 years, 60.9% were male, and 60.7% had private insurance. Overall, 48.9% of patients were transported from an office-based physician practice and 25.1% were transported from UC. Almost one-half (48.7%) of ALS patients received an EMS intervention or medication, as did 4.41% of BLS patients. Respiratory distress was the most common reason for transport (46.9%). Supplemental oxygen was the most common EMS intervention and albuterol was the most administered EMS medication. There was no significant association between level of transport and ED disposition (P = .23). The in-patient admission rate for transported patients was significantly higher than the general ED admission rate (P <.001).

CONCLUSION: This study demonstrates that pediatric patients transferred via EMS after activation of the 9-1-1 system from UC and medical offices are more acutely ill than the general pediatric ED population and are likely sicker than the general pediatric EMS population. Paramedics appear to be making appropriate level-of-care transport decisions.

PMID:37877361 | DOI:10.1017/S1049023X23006544

Clin Trials. 2023 Oct 25:17407745231203327. doi: 10.1177/17407745231203327. Online ahead of print.

ABSTRACT

INTRODUCTION: Developing alternative approaches to evaluating absolute efficacy of new HIV prevention interventions is a priority, as active-controlled designs, whereby individuals without HIV are randomized to the experimental intervention or an active control known to be effective, are increasing. With this design, however, the efficacy of the experimental intervention to prevent HIV acquisition relative to placebo cannot be evaluated directly.

METHODS: One proposed approach to estimate absolute prevention efficacy is to use an HIV exposure marker, such as incident rectal gonorrhea, to infer counterfactual placebo HIV incidence. We formalize a statistical framework for this approach, specify working regression and likelihood-based estimation approaches, lay out three assumptions under which valid inference can be achieved, evaluate finite-sample performance, and illustrate the approach using a recent active-controlled HIV prevention trial.

RESULTS: We find that in finite samples and under correctly specified assumptions accurate and precise estimates of counterfactual placebo incidence and prevention efficacy are produced. Based on data from the DISCOVER trial in men and transgender women who have sex with men, and assuming correctly specified assumptions, the estimated prevention efficacy for tenofovir alafenamide plus emtricitabine is 98.1% (95% confidence interval: 96.4%-99.4%) using the working model approach and 98.1% (95% confidence interval: 96.4%-99.7%) using the likelihood-based approach.

CONCLUSION: Careful assessment of the underlying assumptions, study of their violation, evaluation of the approach in trials with placebo arms, and advancement of improved exposure markers are needed before the HIV exposure marker approach can be relied upon in practice.

PMID:37877356 | DOI:10.1177/17407745231203327

Psychogeriatrics. 2023 Oct 25. doi: 10.1111/psyg.13037. Online ahead of print.

ABSTRACT

BACKGROUND: Demoralization can cause impairments across all life aspects of cancer patients. Cancer patients are also vulnerable during their survivorship. The purpose of this review is to examine the risk of demoralization and associated risk factors among cancer survivors who have completed their primary anti-cancer treatment or time since diagnosis ≥5 years without recurrence.

METHODS: We searched databases of PubMed, Cochrane, Embase, PsycINFO and ClinicalTrial.gov to identify eligible studies which reported the demoralization level among cancer survivors. A random-effect meta-analysis model was used for calculating mean demoralization level. Heterogeneity was evaluated by I² statistics. Funnel plots and Egger’s regression tests were performed for checking publication bias. We used one-study-removed method for sensitivity analysis. Subgroup analysis was also done to examine the difference of demoralization level between cancer types. Meta-regression was performed to reveal risk factors of demoralization.

RESULTS: A meta-analysis of 12 articles involving 2902 cancer survivors was conducted. The mean demoralization score among cancer survivors was 25.98 (95% CI: 23.53-28.43). Higher demoralization level was seen in participants with older age, higher female ratio, higher married/living together status ratio and higher patient health questionnaire-9 score. The literature review revealed correlations between demoralization and suicide risk, anxiety and quality of life. No consistent correlation between demoralization and post-traumatic stress symptoms could be seen.

CONCLUSIONS: High demoralization level is noticed among cancer survivors. Risks for females, elder patients or breast cancer survivors are identified. More longitudinal or interventional studies for cancer survivors’ demoralization are expected in the future.

PMID:37877340 | DOI:10.1111/psyg.13037

J Forensic Sci. 2023 Oct 25. doi: 10.1111/1556-4029.15405. Online ahead of print.

NO ABSTRACT

PMID:37877323 | DOI:10.1111/1556-4029.15405