Robust Multiple Linear Regression Research Articles

Exploring Factors Affecting Students' Deep Approach to Learning in Higher Education: An Empirical Study

Abstract: Survey responses from 858 undergraduates were examined to determine the key factors affecting students' deep approach to learning at two public institutions. Principal component analysis was adopted to eliminate multicollinearity among factors and extract the key influencing factors. A robust multiple linear regression model was built to explore the collective and individual impacts of the key factors on students' deep approach to learning. Data analysis revealed that institutions should put emphasis on 13 key factors that had significant positive influences on students' deep approach to learning, with the strongest impact (β = 0.695, p < .001) coming from educational goals emphasizing synthesizing, analyzing, evaluating information or experience, and problem-solving; and the weakest impact (β = 0.014, p < .001) related to discipline.

Deficits in naming pictures of objects are associated with glioma infiltration of the inferior longitudinal fasciculus: A study with diffusion MRI tractography, volumetric MRI, and neuropsychology.

It has been suggested that the inferior longitudinal fasciculus (ILF) may play an important role in several aspects of language processing such as visual object recognition, visual memory, lexical retrieval, reading, and specifically, in naming visual stimuli. In particular, the ILF appears to convey visual information from the occipital lobe to the anterior temporal lobe (ATL). However, direct evidence proving the essential role of the ILF in language and semantics remains limited and controversial. The first aim of this study was to prove that patients with a brain glioma damaging the left ILF would be selectively impaired in picture naming of objects; the second aim was to prove that patients with glioma infiltrating the ATL would not be impaired due to functional reorganization of the lexical retrieval network elicited by the tumor. We evaluated 48 right-handed patients with neuropsychological testing and magnetic resonance imaging (MRI) before and after surgery for resection of a glioma infiltrating aspects of the left temporal, occipital, and/or parietal lobes; diffusion tensor imaging (DTI) was acquired preoperatively in all patients. Damage to the ILF, inferior frontal occipital fasciculus (IFOF), uncinate fasciculus (UF), arcuate fasciculus (AF), and associated cortical regions was assessed by means of preoperative tractography and pre-/pos-toperative MRI volumetry. The association of fascicles damage with patients' performance in picture naming and three additional cognitive tasks, namely, verbal fluency (two verbal non-visual tasks) and the Trail Making Test (a visual attentional task), was evaluated. Nine patients were impaired in the naming test before surgery. ILF damage was demonstrated with tractography in six (67%) of these patients. The odds of having an ILF damage was 6.35 (95% CI: 1.27-34.92) times higher among patients with naming deficit than among those without it. The ILF was the only fascicle to be significantly associated with naming deficit when all the fascicles were considered together, achieving an adjusted odds ratio of 15.73 (95% CI: 2.30-178.16, p = .010). Tumor infiltration of temporal and occipital cortices did not contribute to increase the odd of having a naming deficit. ILF damage was found to be selectively associated with picture naming deficit and not with lexical retrieval assessed by means of verbal fluency. Early after surgery, 29 patients were impaired in naming objects. The association of naming deficit with percentage of ILF resection (assessed by 3D-MRI) was confirmed (beta = -56.78 ± 20.34, p = .008) through a robust multiple linear regression model; no significant association was found with damage of IFOF, UF or AF. Crucially, postoperative neuropsychological evaluation showed that naming scores of patients with tumor infiltration of the anterior temporal cortex were not significantly associated with the percentage of ILF damage (rho = .180, p > .999), while such association was significant in patients without ATL infiltration (rho = -.556, p = .004). The ILF is selectively involved in picture naming of objects; however, the naming deficits are less severe in patients with glioma infiltration of the ATL probably due to release of an alternative route that may involve the posterior segment of the AF. The left ILF, connecting the extrastriatal visual cortex to the anterior region of the temporal lobe, is crucial for lexical retrieval on visual stimulus, such as in picture naming. However, when the ATL is also damaged, an alternative route is released and the performance improves.

Atypical maternal interaction is associated with elevated levels of hair cortisol in children.

The quality of maternal caregiving is an important factor in the healthy development of a child. One consequence of prolonged insensitive and atypical maternal interaction behavior (e.g., withdrawing from interactions with the child and role-reversal, i.e., the takeover of the parental role or parts of it by the child) in mother-child-dyads can cause alteration of the child's stress response system. Higher salivary cortisol concentrations were reported in infants and toddlers directly after negative interactions with their parents. However, no study to date has examined the association between atypical maternal interaction behavior and hair cortisol concentrations (HCC) in infants. Here, we studied the association of maternal interaction behavior with HCC of the child. Mother-child dyads (N = 112) participated in the longitudinal study My Childhood-Your Childhood. The AMBIANCE scale and its subscales were used to assess atypical maternal interaction behavior during the Strange Situation Procedure. Chronic stress levels in the child were assessed by HCC of 3 cm hair strands at the age of 12 months. Maternal educational level (operationalized in highest education level) served as a control variable. Robust multiple linear regression analyses revealed that role/boundary confusion was associated with HCC, i.e., the higher atypical interaction behavior of the mother the higher the HCC in the children. By measuring hair cortisol in this study, it is possible to determine the average long-term activity of the child's stress response system.Thus, atypical maternal interaction behavior could be a risk factor for persistent stress in children, contributing to a higher risk for negative health outcomes in later life. The results of this study highlight the importance of early intervention programs that focus on the relationship between mother and child.

Understanding the variations in dielectric properties of mustard (Brassica nigra L.) and argemone (Argemone mexicana) oil blends at different temperatures.

Mustard oil is the most commonly adulterated edibleoil, invariably with argemone oil. This study was aimed to develop a parallel plate capacitive sensor for measurement of dielectric properties of pure mustard oil, pure argemone oil and their blends (25, 50 and 75%) at five levels of varying temperature (10 to 50°C). The effect of blend ratio and temperature on the selected dielectric properties of oil-capacitance (C), dielectric loss tangent (tanδ), dielectric constant ( ), dielectric loss factor ( ) and electrical conductivity (σ) were investigated. It was observed that composition of the individual oils in terms of moisture and fatty acids influenced the physical and dielectric properties. The sensor was used to relate the dielectric properties of oil samples with blend ratio and temperature by means of statistically significant (p < 0.05) and robust (R 2 > 0.8) multiple linear regression model. The effect of temperature on C and was negative, while it was otherwise for tanδ, and σ. Increase in argemone oil content in the blends, increased the dielectric measures due to the associated changes in the physical and chemical properties. The capacitive sensor could distinctly identify mustard oil, argemone oil and its blends on the basis of dielectric properties.

Proposed Hybrid Method for Wavelet Shrinkage with Robust Multiple Linear Regression Model With Simulation Study

This study compares the proposed hybrid method (wavelet robust M-estimation) to the traditional method (wavelet ordinary least square) when there are de-noising or outlier problems for estimating multiple linear regression models using the statistical criterion root mean square error (RMSE). According to simulated and real data, the proposed hybrid method (wavelet robust M-estimation) is better than the classical method (Wavelet Ordinary Least Square) and more accurate. The root mean square error of the proposed hybrid method (wavelet robust M-estimation) is less than the Wavelet Ordinary Least Square. Therefore, it is recommended to use the hybrid proposed method to reduce the problem of outliers and de-noise data.

Proposed Hybrid Method for Wavelet Shrinkage with Robust Multiple Linear Regression Model

This study compares the proposed hybrid method (wavelet robust M-estimation) to the traditional method (wavelet ordinary least square) when there are de-noising or outlier problems for estimating multiple linear regression models using the statistical criterion root mean square error (RMSE). According to simulated and real data, the proposed hybrid method (wavelet robust M-estimation) is better than the classical method (Wavelet Ordinary Least Square) and more accurate. The root mean square error of the proposed hybrid method (wavelet robust M-estimation) is less than the Wavelet Ordinary Least Square. Therefore, it is recommended to use the hybrid proposed method to reduce the problem of outliers and de-noise data.

Worry Modifies the Relationship between Locus Coeruleus Activity and Emotional Mnemonic Discrimination.

Background: The locus coeruleus (LC) plays a critical role in modulating emotional memory performance via widespread connections to the medial temporal lobe (MTL). Interestingly, both the LC and MTL are affected during aging. Therefore, we aimed to investigate whether worry during cognitive aging changes the relationship between memory performance and the neural activity patterns during an emotional memory task. Methods: Twenty-eight participants aged 60–83 years from the Maastricht Aging study conducted an emotional mnemonic discrimination task during a 7T fMRI-scan. We performed a robust multiple linear regression to examine the association between worry and mnemonic memory performance under different levels of arousal. Subsequently, we examined if worry modifies the relationship between neuronal activity and mnemonic memory performance. Results: We observed that under low arousal, only participants with low compared to high levels of worry benefitted from additional LC activity. Under high arousal, additional LC activity was associated with lower mnemonic memory performance. Conclusion: Our results suggest there might be an optimal involvement of the NA-system for optimal memory discrimination performance, as we observed that under low levels of worry and with lower levels of arousal, higher LC activity might be needed to achieve similar levels of optimal memory performance as achieved under higher arousal when LC activity remained lower.

Effect of therapeutic regimens and polypharmacy on health-related quality of life of people with multiple myeloma: a cross-sectional study in Belo Horizonte, Brazil

Objective Multiple myeloma (MM) is an incurable hematological cancer and its treatment is geared to promote better Health-Related Quality of Life (HRQoL). We aimed to assess HRQoL and compare scores between variables on therapeutic regimens and polypharmacy in MM patients. Methods This cross-sectional study was performed from April/2019 to February/2020 in Belo Horizonte, Brazil. HRQoL scores were obtained by the QLQ-C30 and QLQ-MY20 instruments. Data were retrieved from interviews and medical records. Therapeutic regimens were grouped into thalidomide-containing regimens; bortezomib-containing regimens; bortezomib and thalidomide-containing regimens; other therapeutic regimens, and remission group. We performed univariate analyses by the Mann-Whitney method and adopted the Kruskal-Wallis test for multiple comparisons. Robust multiple linear regression was used to determine the association between independent variables and the HRQoL scores. Results The sample included 225 participants and most patients (65.3%) were on active treatment and had worse scores concerning future perspective. Polypharmacy was associated with worse scores on all scales in the univariate analyses. We observed a difference in the global health and body image (p < .05) scales in the multiple comparisons with therapeutic regimens. The global health scale difference was found between groups with other regimens and the remission group (p < .05). The difference between the bortezomib and thalidomide-containing regimens and remission group was not statistically significant (p = .077) in the body image scale. The multiple linear regression maintained the association of polypharmacy with worse HRQoL scores. Conclusion We identified an independent association between HRQoL and polypharmacy in MM patients. However, there was no difference between the evaluated regimens, suggesting they are equivalent in Brazil about HRQoL.

The Neighborhood Food Environment and the Onset of Child-Hood Obesity: A Retrospective Time-Trend Study in a Mid-sized City in China.

Nowadays, obesity and its associated chronic diseases have become a steadily growing public health problem, spreading from the older to younger age groups. Studies have contended that the built environment, particularly the food environment and walkability, may contribute to the prevalence of childhood obesity. In Asian countries which are characterized by rapid urbanization, high population density and oriental diets, little is known about how such urban built environment affects the onset of childhood obesity. This study juxtaposes the effect of food environment, walkability, and outdoor activity spaces at the neighborhood level upon childhood body weight in a mid-sized city in China. This observational study utilizes a retrospective time-trend study design to examine the associations between neighborhood built environment and children's body weight in Zhanjiang City, a mid-sized city in Guangdong Province, China. Robust multiple linear and logistic regression models were used to estimate associations between the built environments and child BMI and weight status (i.e., overweight/obesity and obesity only). This study finds that: (1) Western-style fast food and Chinese-style fast food have divergent impacts on childhood body weight. At neighborhood level, while increased exposure to Western-style fast food may increase child BMI and the risk of overweight and obesity, increased exposure to Chinese-style fast food, on the contrary, may reduce child BMI and the risk of overweight and obesity, indicating a positive health impact of Chinese-style fast food. (2) However, the positive health impacts brought about by Chinese-style fast food, walkable environments and accessible traditional fruit/vegetable markets have gradually disappeared in recent years. This study is among the first to simultaneously consider the divergent and changing impact of food environment upon childhood body weight in urban China. The findings provide important implications for healthy city design and the management of food retail industry in addressing the obesity epidemic in younger generations living in Asian cities. As prominent differences exist in food culture between Asian and Western cities, more attention should be paid to healthy food environment in future studies and related urban planning strategies formulation.

Factors associated with nursing workload in three intensive care units.

To determine the nursing workload in intensive care units (ICUs) and the factors associated with the Nursing Activities Score (NAS). An analytical cross-sectional study was carried out in three ICUs in Bucaramanga, Colombia, between February 2018 and February 2020. The nursing workload was estimated based on the NAS. A descriptive and bivariate analysis stratified by ICU was performed using a robust multiple linear regression model, and the factors associated with the nursing workload (p < 0.05) were estimated. In this study, 362 records were included. The median NAS was 68.1 points (Q1:47.2-Q3:116.7). APACHE II (β = 3.13, CI: 95% 2.28; 3.98), days of stay in ICU ≥3 (β = 16.78, CI: 95% 6.15; 27.41), surgery provenance service (β = 22.31, CI: 95% 9.76; 34.86), and traumatology and emergencies diagnostic category (β = 33.72, CI 95%: 9.90; 57.53) were associated with high NAS scores. The nursing staff spend approximately 70% of their time on a single patient, and administrative work takes up most of their time. Hospital stays of longer than 3 days, high APACHE II score, coming from the surgery department, and having a diagnosis of trauma and emergency were associated with a high workload.

Measuring violence perpetration: Stability of teachers’ self-reports before and after an anti-violence training in Cote d’Ivoire

BackgroundEpidemiological studies of interpersonal violence commonly use self-reported violence perpetration as an outcome measure, but few studies have investigated the stability of and influences on self-reports. ObjectiveTo assess changes in teachers’ self-reported use of physical violence against students before and after a one-day violence prevention training, and factors associated with changed reports in Cote d’Ivoire. MethodsBefore and after the training, 157 teachers completed surveys containing 32 questions adapted from the ICAST-CI. Changes in physical violence usage were summarized over lifetime, past school term, and past-week timeframes, and the consistency in responses assessed via intraclass correlation coefficients (3,k), percent agreement, and kappa statistics. Factors associated with changed reports were assessed using robust multiple linear regression with 1,000 bootstrapped replications. ResultsAlthough reports before and after the training should have remained constant, the proportion of teachers reporting 1+ act of violence dropped substantially (lifetime: 73% to 47%). Most teachers (73%) changed 1+ response. Kappa for individual items showed ranging disagreement (lifetime: 0.275-0.795). Variables significantly associated with greater numbers of changed reports included: greater mental health distress (lifetime: beta = 1.061, 95% CI = 0.229, 2.404), older age (past school term: beta = 0.067, 95% CI = 0.018, 0.113); and variables targeted during training, including increasing awareness of consequences of violence (past week: beta = 0.241, 95% CI = 0.046, 0.435) and decreasing acceptance of physical discipline practices in schools (past school term: beta= -0.169, 95% CI= -0.338, -0.045). ConclusionsInterpreting self-reports of violence perpetration requires caution. Formal investigations into reliability and validity of self-reported violence perpetration and victimization are needed.

Abstract P023: Relationship Between TNF-α And SBP In The Baseline Cohort Of The Dietary Approaches To Stop Hypertension (DASH)-Sodium Trial

Hypertension (HTN) is a leading global noncommunicable cause of mortality and dietary salt is the most common modifiable risk factor for HTN. Evidence suggests that tumor necrosis factor alpha (TNF-α) modulates mechanisms that may contribute to salt-sensitive hypertension (SSHT). We conducted a secondary analysis of the baseline cohort of the DASH-Sodium trial, to explore the relationship between TNF-α and systolic blood pressure (SBP) in subjects categorized by race, sex, and baseline blood pressure. Urinary TNF-α levels adjusted for creatinine (pg/mg) were measured in (91%) (374 of 412) subjects ingesting high salt (150 mmol) and control diet for 2 weeks prior to randomization. Descriptive analyses were used to determine the sample prevalence of demographic, laboratory, and outcome variables, and bivariate analyses were used to check for highly correlated variables. Robust multiple linear regression was used to evaluate the association of TNF-α and SBP with and without covariates, p &lt; 0.05. SBP, urinary sodium and potassium adjusted for creatinine, and 24-hour urine volume were positively associated with TNF-α, whereas African American, male, and increasing waist circumference exhibited negative associations with TNF-α, p &lt; 0.05. Predicted TNF-α increased from 22.7 (19.3,26.8) to 33.2 (26.9,41.0) pg/mg with increasing SBP (100 to 180 mm Hg). TNF-α was 25.4 (23.7, 27.1) pg/mg for AA vs. 28.9 (27.2, 30.8) pg/mg for non-AA, and 24.2 (22.6, 25.9) for males vs. (27.3, 30.7) pg/mg for females, respectively. TNF-α increased from 22.3 (20.3, 24.5) to 46.8 (36.1, 60.7) pg/mg as urinary potassium increased from 10 to 100 mg/g, and from 22.7 (20.3, 25.5) to 33.1 (29.0, 37.8) pg/mg as urinary sodium increased from 10 to 250 mg/g. There was a statistically significant interaction between urinary sodium and potassium: TNFα increased to a greater extent with increasing urinary potassium at a lower level of urinary sodium (-1 SD),16.7 (14.0, 20.2) to 38.1 (31.3, 47.3) pg/mg compared to that at higher urinary sodium levels (+1SD), 24.4 (21.0, 28.4) to 35.2 (30.9, 40.1) pg/mg. These results suggest that TNF-α may regulate ion transport mechanisms that contribute to differences in potassium handling and changes in sodium and potassium excretion observed in SSHT.

Localized linear regression methods for estimating monthly precipitation grids using elevation, rain gauge, and TRMM data

Accurate estimation of the spatial distribution of precipitation is crucial for hydrologic modeling. To achieve the realistic estimation of precipitation, developing a ground-based observatory system is a costly and time-consuming strategy compared with other solutions such as using a combination of satellite- and ground-based observations. In this paper, to improve the estimation accuracy of spatial precipitation variation, various linear regression methods were used that combine digital elevation model (DEM) data, rain gauge observations, and Tropical Rainfall Measuring Mission (TRMM) products. Specifically, fuzzy cluster-based linear regression (FCLR), local multiple linear regression using historical similarity (LMLR-HS), model tree (MT), and moving least squares (MLS) were used in the proposed methodology based on local data behavior. The results were compared with those obtained from multiple linear regression (MLR) methods including simple multiple linear regression (SMLR), robust multiple linear regression (RMLR), and generalized linear model (GLM) for monthly precipitation estimation. The study area was Namak Lake watershed, one of the largest watersheds in Iran. The results, estimated for wet and dry years (years 1999 and 2003, respectively), show superiority of local linear regression methods over the other linear methods. Based on the statistical metrics used for assessing the quality the results, FCLR and MLS outperformed other tested methods.

Time to conception and the menstrual cycle: an observational study of fertility app users who conceived

The objective of this research was to evaluate the association between menstrual cycle characteristics (cycle length, cycle-length variability, and their interaction) and the amount of time it takes women to conceive using a robust multiple linear regression. Participants downloaded Ovia Fertility in 2015 indicated that they had just started trying to conceive, and reported conception within 12 months (n = 45,360, adjusted model n = 8835). The average time to conception among women in the adjusted model was 3.94 months (n = 8835). Women with normal cycle lengths (27–29 days) conceived more quickly than women with cycle lengths of 25–26 days (+0.41 months; p < 0.001), 30–31 days (+0.27 months; p < 0.01), 32–33 days (+0.44 months; p < 0.001), and 34+ days (+0.75 months; p < 0.001). Women with regular cycle-length variability (<9 days between cycles) conceived more quickly than women with irregular variability (+0.72 months; p < 0.001). Results of the interaction analysis indicated that, among women with regular cycle-length variability, those with normal cycle length had shorter time to conception than women with either short or long cycle length. The interaction between cycle length and cycle-length variability provided enhanced insights into the amount of time it takes to conceive, compared to either indicator alone.

Personal exposure to PM2.5 constituents associated with gestational blood pressure and endothelial dysfunction

Ambient fine particulate matter (PM2.5) pollution has been implicated in the development of hypertensive disorders of pregnancy. However, evidence on the effects of PM2.5-derived chemical constituents on gestational blood pressure (BP) is limited, and the potential mechanisms underlying the association remain unclear. In this study, we repeated three consecutive 72-h personal air sampling and BP measurements in 215 pregnant women for 590 visits during pregnancy. Individual PM2.5 exposure level was assessed by gravimetric method and 28 PM2.5 chemical constituents were analyzed by ED-XRF method. Plasma biomarkers of endothelial function and inflammation were measured using multiplexed immunoassays. Robust multiple linear regression models were used to estimate the associations among personal PM2.5 exposure and chemical constituents, BP changes (compared with pre-pregnancy BP) and plasma biomarkers. Mediation analyses were performed to evaluate underlying potential pathways. Result showed that exposure to PM2.5 was significantly associated with increases in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) in the early second trimester. Meanwhile, elevated concentration of lead (Pb) constituent in PM2.5 was significant associated with increases in DBP and MAP after adjusting for PM2.5 total mass. PM2.5 and Pb constituent also presented positive associations with plasma biomarkers of endothelial function (ET-1, E-selectin, ICAM-1) and inflammation (IL-1β, IL-6, TNFα) significantly. After multiple adjustment, elevated ET-1 and IL-6 were significantly correlated with increased gestational BP, and respectively mediated 1.24%–25.06% and 7.01%–10.69% of the increased BP due to PM2.5 and Pb constituent exposure. In conclusion, our results suggested that personal exposure to PM2.5 and Pb constituent were significantly associated with increased BP during pregnancy, and the early second trimester might be the sensitive window of PM2.5 exposure. The endothelial dysfunction and elevated inflammation partially mediated the effect of PM2.5 and Pb constituent on BP during pregnancy.

Evaluation of vascular and kidney injury biomarkers in Mexican children exposed to inorganic fluoride

Exposure to inorganic fluoride (F) has been implicated in cardiovascular and kidney dysfunction mainly in adult populations. However, limited epidemiological information from susceptible populations, such as children, is available. In this study we evaluated the relationship of F exposure with some vascular and kidney injury biomarkers in children. A cross-sectional study was conducted in 374 Mexican schoolchildren. Dental fluorosis and F concentrations in the water and urine were evaluated. The glomerular filtration rate (eGFR) and the urinary concentrations of kidney injury molecule 1 (KIM-1) and cystatin-C (uCys-C) were examined to assess kidney injury. The carotid intima media thickness (cIMT) and serum concentrations of vascular adhesion molecule 1 (VCAM-1), intracellular adhesion molecule 1 (ICAM-1), endothelin 1(ET-1) and cystatin-C (sCys-C) were measured to assess vascular alterations. High proportions of children exposed to F were observed (79.7% above 1.2 ppm F in urine) even in the low water F exposure regions, which suggested additional sources of F exposure. In robust multiple linear regression models, urinary F was positively associated with eGFR (β = 1.3, p = 0.015), uCys-C (β = −8.5, p = 0.043), VCAM-1 (β = 111.1, p = 0.019), ICAM-1 (β = 57, p = 0.032) and cIMT (β = 0.01, p = 0.032). An inverse association was observed with uCys-C (β = −8.5, p = 0.043) and sCys-C (β = −9.6, p = 0.021), and no significant associations with ET-1 (β = 0.069, p = 0.074) and KIM-1 (β = 29.1, p = 0.212) were found. Our findings revealed inconclusive results regarding F exposure and kidney injury. However, these results suggest that F exposure is related to early vascular alterations, which may increase the susceptibility of cardiovascular diseases in adult life.

Sector Based Linear Regression, a New Robust Method for the Multiple Linear Regression

This paper describes a new robust multiple linear regression method, which based on the segmentation of the N dimensional space to N+1 sector. An N dimensional regression plane is located so that the half (or other) part of the points are under this plane in each sector. This article also presents a simple algorithm to calculate the parameters of this regression plane. This algorithm is scalable well by the dimension and the count of the points, and capable to calculation with other (not 0.5) quantiles. This paper also contains some studies about the described method, which analyze the result with different datasets and compares to the linear least squares regression. Sector Based Linear Regression (SBLR) is the multidimensional generalization of the mathematical background of a point cloud processing algorithm called Fitting Disc method, which has been already used in practice to process LiDAR data. A robust regression method can be used also in many other fields.

An exploratory study of host polymorphisms in genes that clinically characterize breast cancer tumors and pretreatment cognitive performance in breast cancer survivors.

PurposeInspired by the hypothesis that heterogeneity in the biology of breast cancers at the cellular level may account for cognitive dysfunction symptom variability in survivors, the current study explored relationships between host single-nucleotide polymorphisms (SNPs) in 25 breast cancer-related candidate genes (AURKA, BAG1, BCL2, BIRC5, CCNB1, CD68, CENPA, CMC2, CTSL2, DIAPH3, ERBB2, ESR1, GRB7, GSTM1, MELK, MKI67, MMP11, MYBL2, NDC80, ORC6, PGR, RACGAP1, RFC4, RRM2, and SCUBE2), identified from clinically relevant prognostic multigene-expression profiles for breast cancer, and pretreatment cognitive performance.Patients and methodsThe sample (n=220) was comprised of 138 postmenopausal women newly diagnosed with early stage breast cancer and 82 postmenopausal age- and education-matched healthy controls without breast cancer. Cognitive performance was assessed after primary surgery but prior to initiation of adjuvant chemotherapy and/or hormonal therapy using a comprehensive battery of neuropsychological tests encompassing eight cognitive function composite domains: attention, concentration, executive function, mental flexibility, psychomotor speed, verbal memory, visual memory, and visual working memory. In total, 131 SNPs were included in the analysis. Standard and robust multiple linear regression modeling was used to examine relationships between each domain and the presence or absence of one or more minor alleles for each SNP. Genetic risk/protection scores (GRSs) were calculated for each domain to evaluate the collective effect of possession of multiple risk/protective alleles.ResultsWith the exception of CMC2, MMP11, and RACGAP1, significant (P<0.05) SNP main effect and/or SNP by future prescribed treatment group interactions were observed for every gene between at least one domain and one or more SNPs. All GRSs were found to be significantly (P<0.001) associated with each respective domain score.ConclusionAssociations between host SNPs and computed GRSs and variability in pretreatment cognitive function performance support the study hypothesis, and warrant further investigations to identify biomarkers for breast cancer-related cognitive dysfunction.

Associations between pathologic tumor features and preadjuvant therapy cognitive performance in women diagnosed with breast cancer.

Intertumor heterogeneity has been proposed as a potential mechanism to account for variability in cognitive performance in women diagnosed with breast cancer. The purpose of this study was to explore associations between variation in pathologic tumor features (PTFs) and variability in preadjuvant therapy cognitive performance in postmenopausal women newly diagnosed with early‐stage breast cancer. Participants (N = 329) completed a comprehensive battery of neuropsychological tests to evaluate cognitive performance after primary surgery but prior to initiation of adjuvant anastrozole±chemotherapy. PTF data were abstracted from medical records. Robust multiple linear regression models were fit to estimate associations between individual PTFs and the cognitive function composite domain scores. All models controlled for age, estimated intelligence, and levels of depressive symptoms, anxiety, fatigue, and pain. Diagnosis of a HER2‐positive tumor contributed to poorer verbal (b = −0.287, P = 0.018), visual (b = −0.270, P = 0.001), and visual working (b = −0.490, P < 0.001) memory performance compared to diagnosis of a HER2‐negative tumor. Similarly, as HER2 immunohistochemistry classification score increased, verbal (b = −0.072, P = 0.093), visual (b = −0.081, P = 0.003), and visual working (b = −0.170, P < 0.001) memory performance score decreased. Associations with performance were also noted between location, focality/centricity, hormone receptor expression, cellular proliferation (i.e., Ki67), and Oncotype DX ® Breast Cancer Assay Recurrence Score®.) Our results suggest that certain PTFs related to more aggressive tumor phenotypes or inferior breast cancer prognosis may be implicated in poorer preadjuvant therapy cognitive performance. Follow‐up studies that include a cognitive assessment before primary surgery should be conducted to further delineate the role of intertumor heterogeneity on cognitive performance.

A targeted analysis reveals relevant shifts in the methylation and transcription of genes responsible for bile acid homeostasis and drug metabolism in non-alcoholic fatty liver disease.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is associated with a high risk for liver cirrhosis and cancer. Recent studies demonstrate that NAFLD significantly impacts on the genome wide methylation and expression reporting top hit genes to be associated with e.g. diabetes mellitus. In a targeted analysis we specifically investigate to what extent NAFLD is associated with methylation and transcriptional changes in gene networks responsible for drug metabolism (DM) and bile acid (BA) homeostasis, which may trigger liver and system toxic events.MethodsWe performed a systematic analysis of 73 genes responsible for BA homeostasis and DM based on liver derived methylation and expression data from three cohort studies including 103 NAFLD and 75 non-NAFLD patients. Using multiple linear regression models, we detected methylation differences in proximity to the transcriptional start site of these genes in two NAFLD cohorts and correlated the methylation of significantly changed CpG sites to transcriptional expression in a third cohort using robust multiple linear regression approaches.ResultsWe detected 64 genes involved in BA homeostasis and DM to be significantly differentially methylated. In 26 of these genes, methylation significantly correlated with RNA expression, detecting i.e. genes such as CYP27A1, OSTɑ, and SLC27A5 (BA homeostasis), and SLCO2B1, SLC47A1, and several UGT and CYP genes (DM) to be NAFLD dependently modulated.ConclusionsNAFLD is associated with significant shifts in the methylation of key genes responsible for BA and DM that are associated with transcriptional modulations. These findings have implications for BA composition, BA regulated metabolic pathways and for drug safety and efficacy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2814-z) contains supplementary material, which is available to authorized users.