scholarly journals Early detection of pancreatic ductal adenocarcinomas with an ensemble learning model based on a panel of protein serum biomarkers

2021 ◽  
Author(s):  
Nuno R. Nené ◽  
Alexander Ney ◽  
Tatiana Nazarenko ◽  
Oleg Blyuss ◽  
Harvey E. Johnston ◽  
...  
Keyword(s):  
Early Detection ◽  
Hormone Replacement ◽  
Oral Contraceptive Pill ◽  
Primary Objective ◽  
Ductal Adenocarcinoma ◽  
Sample Collection ◽  
Ovarian Cancer Screening ◽  
Associated Proteins ◽  
Post Menopausal ◽  
Bayesian Averaging

AbstractEarlier detection of pancreatic ductal adenocarcinoma (PDAC) is key to improving patient outcomes, as it is mostly detected at advanced stages which are associated with poor survival. Developing non-invasive blood tests for early detection would be an important breakthrough. The primary objective of the work presented here was to use a unique dataset, that is both large and prospectively collected, to quantify a set of 96 cancer-associated proteins and construct multi-marker models with the capacity to accurately predict PDAC years before diagnosis. The data is part of a nested case control study within UK Collaborative Trial of Ovarian Cancer Screening and is comprised of 219 samples, collected from a total of 143 post-menopausal women who were diagnosed with pancreatic cancer within 70 months after sample collection, and 248 matched non-cancer controls. We developed a stacked ensemble modelling technique to achieve robustness in predictions and, therefore, improve performance in newly collected datasets. With a pool of 10 base-learners and a Bayesian averaging meta-learner, we can predict PDAC status with an AUC of 0.91 (95% CI 0.75 - 1.0), sensitivity of 92% (95% CI 0.54 - 1.0) at 90% specificity, up to 1 year to diagnosis, and at an AUC of 0.85 (95% CI 0.74 - 0.93) up to 2 years to diagnosis (sensitivity of 61%, 95 % CI 0.17 - 0.83, at 90% specificity). These models also use clinical covariates such as hormone replacement therapy use (at randomization), oral contraceptive pill use (ever) and diabetes and outperform biomarker combinations cited in the literature.

Does hormone replacement therapy in post-menopausal women have any effect upon nasal physiology?

2008 ◽  
Vol 122 (7) ◽  
pp. 707-710 ◽  
Author(s):  
D C Wild ◽  
C M Philpott ◽  
C R Wolstenholme ◽  
G E Murty
Keyword(s):  
Hormone Replacement Therapy ◽  
Replacement Therapy ◽  
Hormone Replacement ◽  
Oral Contraceptive Pill ◽  
Life Questionnaire ◽  
Female Hormone ◽  
Menopausal Women ◽  
Nasal Physiology ◽  
Post Menopausal ◽  
Age Range

AbstractBackground:Previous studies have suggested that the female menstrual cycle, pregnancy and the oral contraceptive pill have an effect upon nasal physiology.Objectives:This study aimed to assess the effects upon nasal physiology of female hormone replacement therapy in post-menopausal women. This has not been previously studied.Methods:Twenty post-menopausal women (age range 36 to 70 years; mean age 57.0 years) underwent measurements of the nasal airway, including anterior rhinoscopy, peak nasal inspiratory flow rate, acoustic rhinometry, anterior rhinomanometry, mucociliary clearance time and rhinitis quality of life questionnaire. Measurements of nasal patency were recorded prior to commencing hormone replacement therapy and at a time point 77–195 days (mean 101.9 days) following commencement.Results:There was no statistical difference found for any of the variables, using the paired t-test (p > 0.05 for all).Conclusions:Female hormone replacement therapy has no discernable effect upon nasal physiology and should not be considered a cause of rhinitic symptoms.

BREAST THERMOGRAPHY AS A POTENTIAL NON-CONTACT METHOD IN THE EARLY DETECTION OF CANCER: A REVIEW

2013 ◽  
Vol 13 (02) ◽  
pp. 1330001 ◽  
Author(s):  
MAHNAZ ETEHADTAVAKOL ◽  
EDDIE Y. K. NG
Keyword(s):  
Early Detection ◽  
Tumor Imaging ◽  
Hormone Replacement ◽  
Contact Method ◽  
Invasive Treatment ◽  
Clinical Prognosis ◽  
Breast Thermography ◽  
Utmost Care ◽  
Breast Cells ◽  
Post Menopausal

This review paper discusses recent research achievements in medical thermography with concerns about the possibility of early breast cancer detection. With the advancements in infrared (IR) technology, image processing methods, and the pathophysiological-based knowledge of thermograms, IR screening is sufficiently mature to be utilized as a first-line complement to both health managing and clinical prognosis. In addition, it explains the performance and environmental conditions in identifying thermography for breast tumor imaging under strict indoor controlled environmental circumstances. An irregular thermogram is indicated as a significant biological risk marker for the presence or growth of breast tumors. Breast thermography is completely non-contact, with no form of radiation and compression. It is useful for all women of all ages, for pregnant and breastfeeding women, for women with implants, for women with dense or fibrocystic breasts, for women on hormone replacement therapy, and for pre or post menopausal women. Breast thermography is specifically worthwhile during the early stages of fast tumor growth, which is not yet recognizable by mammography as thermography is a physiological test while mammography is an anatomical one. Often, physiological changes precede anatomical changes. This early detection of irregular tissue liveliness gives breast thermography the potential to be greatly useful and economical as an imaging program and provides the opportunity to apply non-invasive treatment to reform breast tissue activity. The non-radiating nature of thermography also permits repeated images. Thus, changes can be compared over time and the results of protective approaches can be observed to ensure utmost care of breast cells.

scholarly journals Estrogen and COVID-19 symptoms: associations in women from the COVID Symptom Study

2020 ◽  
Author(s):  
Ricardo Costeira ◽  
Karla A Lee ◽  
Benjamin Murray ◽  
Colette Christiansen ◽  
Juan Castillo-Fernandez ◽  
...  
Keyword(s):  
Protective Effect ◽  
Disease Severity ◽  
Hormone Replacement ◽  
Menopausal Status ◽  
Oral Contraceptive Pill ◽  
Premenopausal Women ◽  
Duration Of Treatment ◽  
Menopausal Women ◽  
Post Menopausal ◽  
The Uk

Background: Men and older women have been shown to be at higher risk of adverse COVID-19 outcomes. Animal model studies of SARS-CoV and MERS suggest that the age and sex difference in COVID-19 symptom severity may be due to a protective effect of the female sex hormone estrogen. Females have shown an ability to mount a stronger immune response to a variety of viral infections because of more robust humoral and cellular immune responses. Objectives: We sought to determine whether COVID-19 positivity increases in women entering menopause. We also aimed to identify whether premenopausal women taking exogenous hormones in the form of the combined oral contraceptive pill (COCP) and post-menopausal women taking hormone replacement therapy (HRT) have lower predicted rates of COVID-19, using our published symptom-based model. Design: The COVID Symptom Study developed by Kings College London and Zoe Global Limited was launched in the UK on 24th March 2020. It captured self-reported information related to COVID-19 symptoms. Data used for this study included records collected between 7th May - 15th June 2020. Main outcome measures: We investigated links between COVID-19 rates and 1) menopausal status, 2) COCP use and 3) HRT use, using symptom-based predicted COVID-19, tested COVID-19, and disease severity based on requirement for hospital attendance or respiratory support. Participants: Female users of the COVID Symptom Tracker Application in the UK, including 152,637 women for menopause status, 295,689 for COCP use, and 151,193 for HRT use. Analyses were adjusted for age, smoking and BMI. Results: Post-menopausal women aged 40-60 years had a higher rate of predicted COVID (P=0.003) and a corresponding range of symptoms, with consistent, but not significant trends observed for tested COVID-19 and disease severity. Women aged 18-45 years taking COCP had a significantly lower predicted COVID-19 (P=8.03E-05), with a reduction in hospital attendance (P=0.023). Post-menopausal women using HRT or hormonal therapies did not exhibit consistent associations, including increased rates of predicted COVID-19 (P=2.22E-05) for HRT users alone. Conclusions: Our findings support a protective effect of estrogen on COVID-19, based on positive association between predicted COVID-19 and menopausal status, and a negative association with COCP use. HRT use was positively associated with COVID-19 symptoms; however, the results should be considered with caution due to lack of data on HRT type, route of administration, duration of treatment, and potential comorbidities. Trial registration: The App Ethics has been approved by KCL ethics Committee REMAS ID 18210, review reference LRS-19/20-18210

Abstract 302: Aerobic Exercise Effects on Endothelial Health Status in Pre- and Post Menopausal African American Women

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Heather Grimm ◽  
Jan Jan Kretzschmar ◽  
Sunny Thakkar ◽  
Chenyi Ling ◽  
Keith M Diaz ◽  
...  
Keyword(s):  
African American ◽  
Endothelial Function ◽  
Aerobic Exercise ◽  
African American Women ◽  
Vascular Function ◽  
Hormone Replacement ◽  
Aerobic Exercise Training ◽  
Sample Collection ◽  
American Women ◽  
Post Menopausal

Background: When compared to other racial groups, African American women (AAW) reach menopause at an earlier age and are at an increase risk for CVD and endothelial health complications. A known intervention for the treatment of both CVD and menopausal changes is aerobic exercise training (AEXT). The purpose of this study was to compare the effects of AEXT on endothelial function between pre- and post- menopausal AAW. Methods: Sedentary, non-smoking pre- and post- menopausal AAW not on hormone replacement therapy and free of CVD completed AEXT. Participants exercised at 65% of their VO2max for 40 min, 3 days/wk, for 6 months. Participants completed flow-mediated dilation (FMD) testing and blood sample collection. Endothelial microparticles from plasma samples were analyzed by labeling with late stage apoptotic antibodies CD31+/CD42b- and early phase endothelial dysfunction and endothelial activation CD62E+ and quantified using flow cytometry. Results: No difference in FMD was found between groups before (7.11±1.2 vs. 7.73±0.8 %) or after (10.38±0.2 vs. 9.88±0.6 %) AEXT. Both pre- (7.11±1.2 vs. 10.38±0.2 %, p≤0.005) and post- (7.73±0.8 vs. 9.88±0.6 %, p≤0.043) menopausal women significantly increased FMD after AEXT. CD31+/CD42b- EMPs did not differ between pre- and post-menopausal AAW before (4.52±0.9 vs. 2.9±0.4 events/μL) or after (2.1±0.4 vs. 2.31±0.5e vents/μL) AEXT. CD31+/CD42b- levels significantly decreased in pre-menopausal AAW (4.52±0.9 vs. 2.1±0.4 events/μL, p≤0.015) after AEXT. CD62E+ EMPS were not different between pre- and post-menopausal groups before (44±8.5 vs. 42.5±9 events/μL) or after (26.64±8.4 vs. 19.79±3.2 events/μL) AEXT. Both pre- (44±8.5 vs. 26.6±8.4 events/μL, p≤0.034) and post-menopausal (42.5±9 vs. 19.8±3.2 events/μL, p≤0.008) groups had lower levels of CD62E+ EMPs after AEXT. Discussion: No difference was found in terms of vascular function or health between pre- and post-menopausal AAW. Both groups showed improvements in vascular function and health after AEXT. Our findings suggest AEXT has significant improvements in terms of endothelial function and vascular health in AAW regardless of being a pre- or post-menopausal.

scholarly journals BARD1 Autoantibody Blood Test for Early Detection of Ovarian Cancer

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 969
Author(s):  
Maxim Pilyugin ◽  
Magda Ratasjka ◽  
Maciej Stukan ◽  
Nicole Concin ◽  
Robert Zeillinger ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Early Detection ◽  
Blood Test ◽  
Menopausal Status ◽  
Clinical Samples ◽  
Average Risk ◽  
Healthy Controls ◽  
Cancer Antigen 125 ◽  
Cancer Syndrome ◽  
Ovarian Cancer Screening

Background: Ovarian cancer (OC) is the most lethal gynaecological cancer. It is often diagnosed at an advanced stage with poor chances for successful treatment. An accurate blood test for the early detection of OC could reduce the mortality of this disease. Methods: Autoantibody reactivity to 20 epitopes of BARD1 and concentration of cancer antigen 125 (CA125) were assessed in 480 serum samples of OC patients and healthy controls. Autoantibody reactivity and CA125 were also tested for 261 plasma samples of OC with or without mutations in BRCA1/2, BARD1, or other predisposing genes, and healthy controls. Lasso statistic regression was applied to measurements to develop an algorithm for discrimination between OC and controls. Findings and interpretation: Measurement of autoantibody binding to a number of BARD1 epitopes combined with CA125 could distinguish OC from healthy controls with high accuracy. This BARD1-CA125 test was more accurate than measurements of BARD1 autoantibody or CA125 alone for all OC stages and menopausal status. A BARD1-CA125-based test is expected to work equally well for average-risk women and high-risk women with hereditary breast and ovarian cancer syndrome (HBOC). Although these results are promising, further data on well-characterised clinical samples shall be used to confirm the potential of the BARD1-CA125 test for ovarian cancer screening.

scholarly journals New Onset of DiabetEs in aSsociation with pancreatic ductal adenocarcinoma (NODES Trial): protocol of a prospective, multicentre observational trial

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e037267
Author(s):  
Dóra Illés ◽  
Emese Ivány ◽  
Gábor Holzinger ◽  
Klára Kosár ◽  
M Gordian Adam ◽  
...  
Keyword(s):  
High Risk ◽  
Early Detection ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Clinical Symptoms ◽  
Risk Group ◽  
High Risk Group ◽  
Ductal Adenocarcinoma ◽  
Onset Diabetes ◽  
Dismal Prognosis ◽  
New Onset

IntroductionPancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis with an overall 5-year survival of approximately 8%. The success in reducing the mortality rate of PDAC is related to the discovery of new therapeutic agents, and to a significant extent to the development of early detection and prevention programmes. Patients with new-onset diabetes mellitus (DM) represent a high-risk group for PDAC as they have an eightfold higher risk of PDAC than the general population. The proposed screening programme may allow the detection of PDAC in the early, operable stage. Diagnosing more patients in the curable stage might decrease the morbidity and mortality rates of PDAC and additionally reduce the burden of the healthcare.Methods and analysisThis is a prospective, multicentre observational cohort study. Patients ≥60 years old diagnosed with new-onset (≤6 months) diabetes will be included. Exclusion criteria are (1) Continuous alcohol abuse; (2) Chronic pancreatitis; (3) Previous pancreas operation/pancreatectomy; (4) Pregnancy; (5) Present malignant disease and (6) Type 1 DM. Follow-up visits are scheduled every 6 months for up to 36 months. Data collection is based on questionnaires. Clinical symptoms, body weight and fasting blood will be collected at each, carbohydrate antigen 19–9 and blood to biobank at every second visit. The blood samples will be processed to plasma and analysed with mass spectrometry (MS)-based metabolomics. The metabolomic data will be used for biomarker validation for early detection of PDAC in the high-risk group patients with new-onset diabetes. Patients with worrisome features will undergo MRI or endoscopic ultrasound investigation, and surgical referral depending on the radiological findings. One of the secondary end points is the incidence of PDAC in patients with newly diagnosed DM.Ethics and disseminationThe study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (41085-6/2019). We plan to disseminate the results to several members of the healthcare system includining medical doctors, dietitians, nurses, patients and so on. We plan to publish the results in a peer-reviewed high-quality journal for professionals. In addition, we also plan to publish it for lay readers in order to maximalise the dissemination and benefits of this trial.Trial registration numberClinicalTrials.gov NCT04164602

scholarly journals Metabolomic Biomarkers for the Detection of Obesity-Driven Endometrial Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 718
Author(s):  
Kelechi Njoku ◽  
Amy E. Campbell ◽  
Bethany Geary ◽  
Michelle L. MacKintosh ◽  
Abigail E. Derbyshire ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Early Detection ◽  
Minimally Invasive ◽  
Cancer Detection ◽  
Test Performance ◽  
Female Genital Tract ◽  
Screening Tools ◽  
Normal Endometrium ◽  
Endometrioid Endometrial Cancer ◽  
Post Menopausal

Endometrial cancer is the most common malignancy of the female genital tract and a major cause of morbidity and mortality in women. Early detection is key to ensuring good outcomes but a lack of minimally invasive screening tools is a significant barrier. Most endometrial cancers are obesity-driven and develop in the context of severe metabolomic dysfunction. Blood-derived metabolites may therefore provide clinically relevant biomarkers for endometrial cancer detection. In this study, we analysed plasma samples of women with body mass index (BMI) ≥ 30 kg/m2 and endometrioid endometrial cancer (cases, n = 67) or histologically normal endometrium (controls, n = 69), using a mass spectrometry-based metabolomics approach. Eighty percent of the samples were randomly selected to serve as a training set and the remaining 20% were used to qualify test performance. Robust predictive models (AUC > 0.9) for endometrial cancer detection based on artificial intelligence algorithms were developed and validated. Phospholipids were of significance as biomarkers of endometrial cancer, with sphingolipids (sphingomyelins) discriminatory in post-menopausal women. An algorithm combining the top ten performing metabolites showed 92.6% prediction accuracy (AUC of 0.95) for endometrial cancer detection. These results suggest that a simple blood test could enable the early detection of endometrial cancer and provide the basis for a minimally invasive screening tool for women with a BMI ≥ 30 kg/m2.

scholarly journals The PATHFINDER Study: Assessment of the Implementation of an Investigational Multi-Cancer Early Detection Test into Clinical Practice

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3501
Author(s):  
Lincoln D. Nadauld ◽  
Charles H. McDonnell ◽  
Tomasz M. Beer ◽  
Minetta C. Liu ◽  
Eric A. Klein ◽  
...  
Keyword(s):  
Early Detection ◽  
Test Performance ◽  
Primary Objective ◽  
Diagnostic Evaluation ◽  
Cancer Risk Factors ◽  
Cancer Early Detection ◽  
Diagnostic Resolution ◽  
Multi Center Study ◽  
Diagnostic Pathways ◽  
Prospective Longitudinal

To examine the extent of the evaluation required to achieve diagnostic resolution and the test performance characteristics of a targeted methylation cell-free DNA (cfDNA)-based multi-cancer early detection (MCED) test, ~6200 participants ≥50 years with (cohort A) or without (cohort B) ≥1 of 3 additional specific cancer risk factors will be enrolled in PATHFINDER (NCT04241796), a prospective, longitudinal, interventional, multi-center study. Plasma cfDNA from blood samples will be analyzed to detect abnormally methylated DNA associated with cancer (i.e., cancer “signal”) and a cancer signal origin (i.e., tissue of origin). Participants with a “signal detected” will undergo further diagnostic evaluation per guiding physician discretion; those with a “signal not detected” will be advised to continue guideline-recommended screening. The primary objective will be to assess the number and types of subsequent diagnostic tests needed for diagnostic resolution. Based on microsimulations (using estimates of cancer incidence and dwell times) of the typical risk profiles of anticipated participants, the median (95% CI) number of participants with a “signal detected” result is expected to be 106 (87–128). Subsequent diagnostic evaluation is expected to detect 52 (39–67) cancers. The positive predictive value of the MCED test is expected to be 49% (39–58%). PATHFINDER will evaluate the integration of a cfDNA-based MCED test into existing clinical cancer diagnostic pathways. The study design of PATHFINDER is described here.

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