NOPAPROD Non-Parametric Testing on Projections from Multivariate Data. Applications to near Infrared Spectroscopy in Clinical Studies

2009 ◽  
Vol 17 (2) ◽  
pp. 101-107 ◽  
Author(s):  
Josefina Nyström ◽  
Britta Lindholm-Sethson ◽  
Paul Geladi

Clinical studies may be carried out using non-invasively collected near infrared spectra of patient skin. Two problems encountered are: (1) data reduction to go from thousands of wavelengths to some clinically relevant estimator and (2) getting statistical significance from noisy data with sometimes very skewed distributions. The problem of data reduction can usually be solved by principal component analysis to get a few meaningful components. In the space spanned by these components, a direction of discrimination may have to be found, typically discrimination between treated and control. A visual difference in a score plot is often not enough; statistical significance has to be demonstrated. Once a univariate estimator is found, non-parametric testing can show significant differences, even if the data are noisy and have an unknown and skewed distribution. The NOPRAPOD method com bines the actions of finding a direction in a reduced data space and performing the non-parametric significance testing by producing a disk of significance. Two examples are included. Example one is from a study of diabetes-related neuropathy where it is shown that significant differences show up in the NIR spectra. Example two is from a study of post-operative radiation treatment of breast cancer patients, where it is shown that radiation effects (erythema) and the effect of lotion can be determined with an indication of significance from the NIR spectra.

Breast Care ◽  
2020 ◽  
pp. 1-9
Author(s):  
Rudolf Napieralski ◽  
Gabriele Schricker ◽  
Gert Auer ◽  
Michaela Aubele ◽  
Jonathan Perkins ◽  
...  

<b><i>Background:</i></b> PITX2 DNA methylation has been shown to predict outcomes in high-risk breast cancer patients after anthracycline-based chemotherapy. To determine its prognostic versus predictive value, the impact of PITX2 DNA methylation on outcomes was studied in an untreated cohort vs. an anthracycline-treated triple-negative breast cancer (TNBC) cohort. <b><i>Material and Methods:</i></b> The percent DNA methylation ratio (PMR) of paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time PCR test. Patient samples of routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue and clinical data from 144 TNBC patients of 2 independent cohorts (i.e., 66 untreated patients and 78 patients treated with anthracycline-based chemotherapy) were analyzed. <b><i>Results:</i></b> The risk of 5- and 10-year overall survival (OS) increased continuously with rising PITX2 DNA methylation in the anthracycline-treated population, but it increased only slightly during 10-year follow-up time in the untreated patient population. PITX2 DNA methylation with a PMR cutoff of 2 did not show significance for poor vs. good outcomes (OS) in the untreated patient cohort (HR = 1.55; <i>p</i> = 0.259). In contrast, the PITX2 PMR cutoff of 2 identified patients with poor (PMR &#x3e;2) vs. good (PMR ≤2) outcomes (OS) with statistical significance in the anthracycline-treated cohort (HR = 3.96; <i>p</i> = 0.011). The results in the subgroup of patients who did receive anthracyclines only (no taxanes) confirmed this finding (HR = 5.71; <i>p</i> = 0.014). <b><i>Conclusion:</i></b> In this hypothesis-generating study PITX2 DNA methylation demonstrated predominantly predictive value in anthracycline treatment in TNBC patients. The risk of poor outcome (OS) correlates with increasing PITX2 DNA methylation.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Liping Huang ◽  
Yiyi Zhang ◽  
Yanan Li ◽  
Fanling Meng ◽  
Hongyu Li ◽  
...  

AbstractThe highly immunosuppressive microenvironment after surgery has a crucial impact on the recurrence and metastasis in breast cancer patients. Programmable delivery of immunotherapy-involving combinations through a single drug delivery system is highly promising, yet greatly challenging, to reverse postoperative immunosuppression. Here, an injectable hierarchical gel matrix, composed of dual lipid gel (DLG) layers with different soybean phosphatidylcholine/glycerol dioleate mass ratios, was developed to achieve the time-programmed sequential delivery of combined cancer immunotherapy. The outer layer of the DLG matrix was thermally responsive and loaded with sorafenib-adsorbed graphene oxide (GO) nanoparticles. GO under manually controlled near-infrared irradiation generated mild heat and provoked the release of sorafenib first to reeducate tumor-associated macrophages (TAMs) and promote an immunogenic tumor microenvironment. The inner layer, loaded with anti-CD47 antibody (aCD47), could maintain the gel state for a much longer time, enabling the sustained release of aCD47 afterward to block the CD47-signal regulatory protein α (SIRPα) pathway for a long-term antitumor effect. In vivo studies on 4T1 tumor-bearing mouse model demonstrated that the DLG-based strategy efficiently prevented tumor recurrence and metastasis by locally reversing the immunosuppression and synergistically blocking the CD47-dependent immune escape, thereby boosting the systemic immune responses.


1991 ◽  
Vol 9 (7) ◽  
pp. 1113-1123 ◽  
Author(s):  
D F Hayes ◽  
R Mesa-Tejada ◽  
L D Papsidero ◽  
G A Croghan ◽  
A H Korzun ◽  
...  

Three monoclonal antibodies (MAbs) (DF3, F36/22, CU18) were used to monitor expression of distinct epitopes present within a family of mucin-like, breast carcinoma-associated molecules. Primary tumor specimens from more than 190 stage II breast cancer patients were evaluated for expression of the high molecular weight antigens. With a median follow-up of 6 years, patients whose tumors exhibited high immunoperoxidase staining scores (greater than 50% positive cells) with MAb DF3 had a superior disease-free survival ([DFS] 56% +/- 6% v 37% +/- 5% at 6 years; P = .0088) and overall survival ([OS] 72% +/- 5% v 59% +/- 5% at 6 years; P = .025). Staining scores with the other two antibodies did not correlate with improved prognosis. For MAbs DF3 and CU18, patients whose tumors exhibited predominantly apical cellular reactivity patterns had improved DFS, although differences reached conventional levels of statistical significance only with MAb CU18. In multivariate analyses, the prognostic value of MAb DF3 staining was independent of other identified prognostic factors. Furthermore, the concordance between primary and axillary lymph node metastases staining with each MAb was 73%, 80%, and 85% for MAbs DF3, F36/22, and CU18, respectively. These results suggest that staining with MAb DF3 identifies a group of node-positive women with a relatively favorable prognosis. Expression of the DF3 mucin-like glycoprotein is related to better differentiation, and staining with MAb DF3 provides an accurate and objective estimate of clinical outcome independent of histopathologic evaluation.


2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Noman Naseer ◽  
Nauman Khalid Qureshi ◽  
Farzan Majeed Noori ◽  
Keum-Shik Hong

We analyse and compare the classification accuracies of six different classifiers for a two-class mental task (mental arithmetic and rest) using functional near-infrared spectroscopy (fNIRS) signals. The signals of the mental arithmetic and rest tasks from the prefrontal cortex region of the brain for seven healthy subjects were acquired using a multichannel continuous-wave imaging system. After removal of the physiological noises, six features were extracted from the oxygenated hemoglobin (HbO) signals. Two- and three-dimensional combinations of those features were used for classification of mental tasks. In the classification, six different modalities, linear discriminant analysis (LDA), quadratic discriminant analysis (QDA),k-nearest neighbour (kNN), the Naïve Bayes approach, support vector machine (SVM), and artificial neural networks (ANN), were utilized. With these classifiers, the average classification accuracies among the seven subjects for the 2- and 3-dimensional combinations of features were 71.6, 90.0, 69.7, 89.8, 89.5, and 91.4% and 79.6, 95.2, 64.5, 94.8, 95.2, and 96.3%, respectively. ANN showed the maximum classification accuracies: 91.4 and 96.3%. In order to validate the results, a statistical significance test was performed, which confirmed that thepvalues were statistically significant relative to all of the other classifiers (p< 0.005) using HbO signals.


2018 ◽  
Vol 478 (2) ◽  
pp. 2097-2112 ◽  
Author(s):  
Sirio Belli ◽  
Alessandra Contursi ◽  
Richard I Davies

Author(s):  
Anas Ramadan Al-Masri

The current study aims at recognizing the relationship between the health, family, social, economic and psychological pressures and their relation to psychological hardiness among breast cancer patients. The researcher follows descriptive and explanatory approaches to explain this relationship. The research sample consists of 150 women affected by breast cancer; and researcher used the scale of breast cancer patients’ pressures (prepared by Hijazi, 2012), as well as the scale of psychological hardiness (prepared by Mukhaimer, 1997). Results indicated having a negative correlation between the overall rigidity aspect and the health, family, social, economic and psychological pressures. The study also indicated having health, psychological and social pressures affecting breast cancer patients, having differences of statistical significance in family and psychological pressures refer in the marital status variable to married women while having lack of differences of statistical significance in health, social and economic pressures refer to the children variable. Results also indicated that women affected by breast cancer have psychological hardiness, having a negative correlation between the aspects of commitment and control, and the health, family, social, economic, psychological, having a correlation between the aspect of control and the health and economic pressures, having a negative correlation between the aspect of the challenge and the family, social, economic, psychological, having differences of statistical significance in control referring to the marital status variable for the married women and having differences of statistical significance in control, challenge, commitment referring to the number of children variable.


2020 ◽  
Author(s):  
Jeffrey Peacock ◽  
Dhiraj Sikaria ◽  
Laura Maun-Garcia ◽  
Khosrow Javedan ◽  
Kosj Yamoah ◽  
...  

Abstract Backgrounds: Prostatic artery embolization (PAE) has been well studied as a clinically effective therapy for alleviating lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH). We demonstrate a proof of concept for PAE prior to definitive radiotherapy in patients with prostate cancer.Methods: From 12/2017 to 07/2019, 57 patients underwent PAE for LUTS and BPH. Nine of these patients had PAE for LUTS in the setting of localized prostate cancer prior to receiving radiation. Five of the nine patients received their entire radiotherapy course at our institution and had clinical follow up were included in the analysis. Median follow up was 18 months from the time of PAE. LUTS improvement quantified by IPSS was the primary endpoint and a two tail students T test was used to compare statistical significance. Side effects during radiation were quantified using the CTCAE scoring system. Pre- and post- PAE plans were compared in the five patients that by performing an isovolumetric expansion of the post PAE plan (treated plan) equivalent to the measured volume reduction after PAE. Patient 1 and 2 had prostate and seminal vesicle RT alone while patients 3-5 had prostate with elective nodal coverage. Mean doses to organs at risk were compared between the two plans.Results: The average IPSS score pre-PAE was 17.40 compared to post-PAE of 3.6 (p=0.02). The average IPSS score reduction after PAE was 13.8 (5-30). The average prostatic volume reduction after PAE was 23.14% (7.2% - 47.7%). There were no CTCAE grade 3 (severe) or higher during radiation treatment. Post-PAE plans in patient 1 and 2 had on average 16.7% and 39.8% decrease in mean dose across the bladder, rectum, and penile bulb compared to the pre-PAE plans. There were no appreciable differences in dosimetry in the patients 3-5 who had nodal coverage. There was no biochemical failure in any of the patients.Conclusion: We demonstrate a proof of concept that prostate artery embolization is useful as an adjunctive procedure to alleviate LUTS, achieve significant volume reduction prior to radiation therapy, and decrease radiation related toxicity in the treatment of prostate cancer.


2021 ◽  
Author(s):  
Maryam Vasaghi Gharamaleki ◽  
Seyedeh Zahra Mousavi ◽  
Maryam Owrangi ◽  
Mohammad Javad Gholamzadeh ◽  
Ali-Mohammad Kamali ◽  
...  

Background: Post-chemotherapy cognitive impairment commonly known as "chemobrain" or "chemofog" is a well-established clinical disorder affecting various cognitive domains including attention, visuospatial working memory, executive function, etc. Although several studies have confirmed the chemobrain in recent years, scant experiments have evaluated the potential neurotoxicity of different chemotherapy regimens and agents. In this study, we aimed to evaluate the extent of attention deficits, one of the commonly affected cognitive domains, among breast cancer patients treated with different chemotherapy regimens through neuroimaging techniques. Methods: Breast cancer patients treated with two commonly prescribed chemotherapy regimens, AC-T and TAC, and healthy volunteers were recruited. Near-infrared hemoencephalography (nirHEG) and quantitative electroencephalography (qEEG) assessments were recorded for each participant at rest and during task performance to compare the functional cortical changes associated with each chemotherapy regimen. Results: The qEEG analysis revealed increased power of high alpha/low beta or sensorimotor rhythm (SMR) frequency in left fronto-centro-parietal regions involved in dorsal and ventral attention networks (DAN and VAN) in the AC-T-treated group comparing to the TAC and control group. The AC-T group also had the highest current source density (CSD) values in DAN and VAN-related centers in 10 and 15 Hz associated with the lowest Z-scored FFT coherence in the mentioned regions. Conclusions: The mentioned findings revealed increased cognitive workload and lack of cognitive ease in breast cancer patients treated with the AC-T regimen proposing the presumable neurotoxic sequelae of this chemotherapy regimen in comparison with the TAC regimen.


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