Kernel Regression Coefficients for Practical Significance

Quantitative researchers often use Student’s t-test (and its p-values) to claim that a particular regressor is important (statistically significantly) for explaining the variation in a response variable. A study is subject to the p-hacking problem when its author relies too much on formal statistical significance while ignoring the size of what is at stake. We suggest reporting estimates using nonlinear kernel regressions and the standardization of all variables to avoid p-hacking. We are filling an essential gap in the literature because p-hacking-related papers do not even mention kernel regressions or standardization. Although our methods have general applicability in all sciences, our illustrations refer to risk management for a cross-section of firms and financial management in macroeconomic time series. We estimate nonlinear, nonparametric kernel regressions for both examples to illustrate the computation of scale-free generalized partial correlation coefficients (GPCCs). We suggest supplementing the usual p-values by “practical significance” revealed by scale-free GPCCs. We show that GPCCs also yield new pseudo regression coefficients to measure each regressor’s relative (nonlinear) contribution in a kernel regression.

Co-expression of cancer-testis antigens of MAGE-A6 and MAGE-A11 is associated with tumor aggressiveness in patients with bladder cancer

Melanoma antigen gene (MAGE)-A6 and MAGE-A11 are two of the most cancer-testis antigens overexpressed in various types of cancers. However, the clinical and prognosis value of MAGE-A6 and MAGE-A11 co-expression in the pathophysiology of the bladder is unknown. Three studies were selected from GEO databases in order to introduce the common genes that are involved in bladder cancer. Then immunohistochemical analysis for staining pattern and clinicopathological significance of suggested markers, MAGE-A6 and MAGE-A11, were performed in 199 and 213 paraffin-embedded bladder cancer with long adjacent normal tissues, respectively. A significant and positive correlation was found between both nuclear and cytoplasmic expressions of MAGE-A6 as well as expression of cytoplasmic MAGE-A11 with histological grade, PT stage, lamina propria invasion, and LP/ muscularis (L/M) involvement (all of the p-values in terms of H-score were < 0.0001). Additionally, significant differences were found between both nuclear and cytoplasmic MAGE-A6/MAGE-A11 phenotypes with tumor size (P = 0.007, P = 0.043, respectively), different histological grades, PT stage, LP involvement, and L/M involvement (all of the p-values for both phenotypes were < 0.0001). The current study added the value of these novel markers to the bladder cancer clinical settlement that might be considered as an admirable target for immunotherapy.

Early Postoperative Serum Carcinoembryonic Antigen Is a Stronger Independent Prognostic Factor for Stage II Colorectal Cancer Patients Than T4 Stage and Preoperative CEA

BackgroundSerum carcinoembryonic antigen (CEA) is an important biomarker for diagnosis, prognosis, recurrence, metastasis monitoring, and the evaluation of the effect of chemotherapy in colorectal cancer (CRC). However, few studies have focused on the role of early postoperative CEA in the prognosis of stage II CRC.MethodsPatients with stage II CRC diagnosed between January 2007 and December 2015 were included. Receiver operating characteristic (ROC) curves were used to obtain the cutoff value of early postoperative CEA, CEA ratio and CEA absolute value. The areas under curves (AUCs) were used to estimate the predictive abilities of the CEA and T stage. The stepwise regression method was used to screen the factors included in the Cox regression analysis. Before and after propensity score (PS) - adjusted Cox regression and sensitivity analysis were used to identify the relationship between early postoperative CEA and prognosis. Meta-analysis was performed to verify the results. Kaplan-Meier survival curves were used to estimate the effects of CEA on prognosis.ResultsWe included 1081 eligible patients. ROC curves suggested that the cutoff value of early postoperative CEA was 3.66 ng/ml (P &lt;0.001) and the AUC showed early postoperative CEA was the most significant prognostic marker in stage II CRC (P = 0.0189). The Cox regression and sensitivity analysis before and after adjusting for PS both revealed elevated early postoperative CEA was the strongest independent prognostic factor of OS, DFS, and CSS (P &lt; 0.001). Survival analysis revealed that patients with elevated early postoperative CEA had lower OS (53.62% VS 84.16%), DFS (50.03% VS 86.75%), and CSS (61.77% VS 90.30%) than patients with normal early postoperative CEA (P &lt; 0.001). When the postoperative CEA was positive, the preoperative CEA level showed no significant effect on the patient’s prognosis (all P-values were &gt; 0.05). Patients with a CEA ratio ≤0.55 or CEA absolute value ≤-0.98 had a worse prognosis (all P-values were &lt; 0.001). Survival analysis suggested that adjuvant chemotherapy for stage II CRC patients with elevated early postoperative CEA may improve the CSS (P = 0.040).ConclusionsEarly postoperative CEA was a better biomarker for prognosis of stage II CRC patients than T stage and preoperative CEA, and has the potential to become a high-risk factor to guide the prognosis and treatment of stage II CRC patients.

Synthetic MRI for Stroke: A Qualitative and Quantitative Pilot Study

PurposeSynthetic MR provides quantitative multiparametric data about tissue properties in a fast single-acquisition. We compared synthetic and conventional image quality and investigated synthetic relaxometry of acute and chronic ischemic lesions to support its interest in stroke imaging. MethodsFor this pilot study, we prospectively acquired synthetic and conventional brain MR of 43 consecutive adult patients with suspected stroke. We studied a total of 136 lesions, of which 46 DWI-positive with restricted ADC (DWI+/rADC), 90 white matter T2/FLAIR hyperintensities (WMH), and 430 normal brain regions (NBR). We assessed image quality for lesion definition according to a 3-level score by two readers of different experiences. We compared relaxometry of lesions and regions of interest.Results Synthetic images were superior to their paired conventional images for lesion definition except for sFLAIR (sT1 or sPSIR vs. cT1 and sT2 vs. cT2 for DWI+/rADC and WMH definition; p-values <.001) with substantial to almost perfect inter-rater reliability (κ ranging from 0.711 to 0.932, p-values <.001). We found significant differences in relaxometry between lesions and NBR and between acute and chronic lesions (T1, T2, and PD of DWI+/rADC or WMH vs. mirror NBR; p-values <.001; T1 and PD of DWI+/rADC vs. WMH; p-values of 0.034 and 0.008).Conclusion Synthetic MR may contribute to stroke imaging by fast acquiring consistent relaxometry data and accessible derived images of interest for the study of ischemic lesions.

Effect of Propolis on Precocious Puberty in Female Rats

Introduction: Nutrition and exposure to various chemicals, including environmental pollution, insecticides, and plant phytoestrogens (having oestrogen-like effects), are environmental factors that affect puberty onset. We aimed to identify the effects of propolis on precocious puberty and the reproductive system in prepubertal female rats (ovary, endometrium, breast).Methods: Thirty-four 25-day-old prepubertal female Sprague-Dawley rats were included in the study. Rats were randomly divided into the propolis (n 17) and control groups (n 17). The primary endpoint was the number of rats that developed vaginal opening (It's a sign of puberty) at 12-day follow-up. In addition, the effect of propolis on ovary, uterus and breast tissue was evaluated.Results: Vaginal patency occurred earlier in the propolis group. At the same time, a greater number of rats developed vaginal opening. The number of ovarian follicles (in all follicles), endometrial thickness, and mammary gland secretory gland area were significantly higher in the propolis group than in the control group (p-values <0.001, <0.001, <0.001, respectively). In addition, Ki-67 activity in the endometrium, breast tissue and ovary was more intense in the propolis group compared to the control group (p-values <0.001, <0.001, <0.001, respectively).Conclusion: Propolis triggers precocious puberty in female rats, possibly by interacting with the oestrogen receptor. The mechanism of action of propolis should be considered before prescribing it. In addition, further studies are needed to explore the mechanism of action of propolis and to determine the component of propolis that triggers puberty.

Differentiating perinatal Insomnia Disorder and sleep disruption: A longitudinal study from pregnancy to 2 years postpartum

Study Objectives Insomnia Disorder diagnoses require persistent sleep complaints despite “adequate sleep opportunity”. Significant perinatal sleep disruption makes this diagnosis challenging. This longitudinal study distinguished between Insomnia Disorder and Perinatal Sleep Disruption and their sleep and mental health correlates. Methods 163 nulliparous females (age M±SD=33.35±3.42) participating in a randomised-controlled trial repeated the Insomnia Disorder module of the Duke Structured Interview for Sleep Disorders and PROMIS measures for sleep and mental health at 30 and 35 weeks’ gestation, and 1.5, 3, 6, 12, and 24 months postpartum (944 interviews, 1009 questionnaires completed). We compared clinical features when DSM-5 Insomnia Disorder criteria were: (1) met (Insomnia Disorder), (2) not met only because of the sleep opportunity criteria (Perinatal Sleep Disruption), and (3.) not met due to other criteria (Low Complaint). Results Proportions of Insomnia Disorder were 16.0% and 19.8% during early and late third trimester, and ranged 5.3-11.7% postpartum. If the sleep opportunity criteria were not considered, rates of Insomnia would be 2-4 times higher (21.4-40.4%) across time-points. Mixed effects models adjusting for covariates showed that compared to Low Complaint, both Insomnia Disorder and Perinatal Sleep Disruption scored significantly higher on insomnia and sleep disturbance scales, sleep effort, and sleep-related impairments (p-values&lt;.01), but depression and anxiety were comparable (p-values&gt;.12). Conclusion Assessing sleep complaints without considering sleep opportunity can result in over-diagnosis of Insomnia Disorder in the perinatal periods. Insomnia Disorder and perinatal sleep disruption were associated with adverse sleep and mood outcomes, and need to be carefully differentiated and appropriately addressed.

The additive effect of essential hypertension on coronary artery plaques in type 2 diabetes mellitus patients: a coronary computed tomography angiography study

Background The effect of comorbid hypertension and type 2 diabetes mellitus (T2DM) on coronary artery plaques examined by coronary computed tomography angiography (CCTA) is not fully understood. We aimed to comprehensively assess whether comorbid hypertension and T2DM influence coronary artery plaques using CCTA. Materials and methods A total of 1100 T2DM patients, namely, 277 normotensive [T2DM(HTN−)] and 823 hypertensive [T2DM(HTN +)] individuals, and 1048 normotensive patients without T2DM (control group) who had coronary plaques detected on CCTA were retrospectively enrolled. Plaque type, coronary stenosis, diseased vessels, the segment involvement score (SIS) and the segment stenosis score (SSS) based on CCTA data were evaluated and compared among the groups. Results Compared with patients in the control group, the patients in the T2DM(HTN−) and T2DM(HTN +) groups had more partially calcified plaques, noncalcified plaques, segments with obstructive stenosis, and diseased vessels, and a higher SIS and SSS (all P values < 0.001). Compared with the control group, T2DM(HTN +) patients had increased odds of having any calcified and any noncalcified plaque [odds ratio (OR) = 1.669 and 1.278, respectively; both P values < 0.001]; both the T2DM(HTN-) and T2DM(HTN +) groups had increased odds of having any partially calcified plaque (OR = 1.514 and 2.323; P = 0.005 and P < 0.001, respectively), obstructive coronary artery disease (CAD) (OR = 1.629 and 1.992; P = 0.001 and P < 0.001, respectively), multivessel disease (OR = 1.892 and 3.372; both P-values < 0.001), an SIS > 3 (OR = 2.233 and 3.769; both P values < 0.001) and an SSS > 5 (OR = 2.057 and 3.580; both P values < 0.001). Compared to T2DM(HTN−) patients, T2DM(HTN +) patients had an increased risk of any partially calcified plaque (OR = 1.561; P = 0.005), multivessel disease (OR = 1.867; P < 0.001), an SIS > 3 (OR = 1.647; P = 0.001) and an SSS > 5 (OR = 1.625; P = 0.001). Conclusion T2DM is related to the presence of partially calcified plaques, obstructive CAD, and more extensive coronary artery plaques. Comorbid hypertension and diabetes further increase the risk of partially calcified plaques, and more extensive coronary artery plaques.