Smartphone-based application to control and prevent overweight and obesity in children: design and evaluation.

BACKGROUND: Obesity is a multifaceted condition that impacts individuals across various age, racial, and socioeconomic demographics, hence rendering them susceptible to a range of health complications and an increased risk of premature mortality. The frequency of obesity among adolescent females in Iran has exhibited an increase from 6 to 9%, while among boys, it has risen from 2 to 7%. Due to the increasing prevalence and advancements in technology, the primary objective of this study was to develop and evaluate a smartphone-based app that would serve as an educational tool for parents about the matter of childhood overweight and obesity. Additionally, the app aimed to enhance parents' capacity to effectively address and manage their children's weight-related concerns. METHODS: The design of the present study is of an applied-developmental type. In the first phase, the content of related smartphone-based app was determined based on the needs identified in similar studies and the findings of a researcher-made questionnaire. The versions of the app were designed in the android studio 3 programming environment, using the Java 8 programming language and SQLite database. Then, in order to evaluate the app's usability, ease of access, and different features, the standard usability evaluation questionnaire and the user satisfaction questionnaire (QUIS) were completed by the users. RESULTS: The developed app has five main sections: the main page, recommendation section (with eight parts), charts over the time, child psychology, and reminders for each user. The designed app was given to 20 people including nutritionists and parents with children under 18 years of age for conducting usability evaluation. According to the scores of participants about the usability evaluation of the app, it can be concluded that groups participating in the study could use the program, and they rated the app at a "good" level. Overall performance of the app, screen capabilities, terms and information of the program, learnability, and general features are scored higher than 7.5 out of 9. CONCLUSION: By using this app, people can become familiar with the causes and symptoms of weight imbalance and manage their weight as best as possible. This app can be considered as a model for designing and creating similar broader systems and programs for the prevention, management, treatment and care of diseases, which aim to help control diseases as much as possible and increase the quality of life and reduce complications for be patients.

Effects of Transcranial Direct Current Stimulation on Attentional Bias to Methamphetamine Cues and Its Association With EEG-Derived Functional Brain Network Topology.

BACKGROUND: Although transcranial direct current stimulation (tDCS) has shown to potentially mitigate drug craving and attentional bias to drug-related stimuli, individual differences in such modulatory effects of tDCS are less understood. In this study, we aimed to investigate a source of the inter-subject variability in the tDCS effects that can be useful for tDCS-based treatments of individuals with methamphetamine (MA) use disorder (IMUD). METHODS: Forty-two IMUD (all male) were randomly assigned to receive a single-session of either sham or real bilateral tDCS (anodal right/cathodal left) over the dorsolateral prefrontal cortex. The tDCS effect on MA craving and biased attention to drug stimuli were investigated by quantifying EEG-derived P3 (a measure of initial attentional bias) and late positive potential (LPP; a measure of sustained motivated attention) elicited by these stimuli. To assess the association of changes in P3 and LPP with brain connectivity network (BCN) topology, the correlation between topology metrics, specifically those related to the efficiency of information processing, and the tDCS effect was investigated. RESULTS: The P3 amplitude significantly decreased following the tDCS session, whereas the amplitudes increased in the sham group. The changes in P3 amplitudes were significantly correlated with communication efficiency measured by BCN topology metrics (r = -0.47, P = .03; r = -0.49, P = .02). There was no significant change in LPP amplitude due to the tDCS application. CONCLUSIONS: These findings validate that tDCS mitigates initial attentional bias, but not the sustained motivated attention, to MA stimuli. Importantly, however, results also show that the individual differences in the effects of tDCS may be underpinned by communication efficiency of the BCN topology, and therefore, these BCN topology metrics may have the potential to robustly predict the effectiveness of tDCS-based interventions on MA craving and attentional bias to MA stimuli among IMUD.

VTRNA2-1: Genetic Variation, Heritable Methylation and Disease Association.

VTRNA2-1 is a metastable epiallele with accumulating evidence that methylation at this region is heritable, modifiable and associated with disease including risk and progression of cancer. This study investigated the influence of genetic variation and other factors such as age and adult lifestyle on blood DNA methylation in this region. We first sequenced the VTRNA2-1 gene region in multiple-case breast cancer families in which VTRNA2-1 methylation was identified as heritable and associated with breast cancer risk. Methylation quantitative trait loci (mQTL) were investigated using a prospective cohort study (4500 participants with genotyping and methylation data). The cis-mQTL analysis (334 variants ± 50 kb of the most heritable CpG site) identified 43 variants associated with VTRNA2-1 methylation (p < 1.5 × 10-4); however, these explained little of the methylation variation (R2 < 0.5% for each of these variants). No genetic variants elsewhere in the genome were found to strongly influence VTRNA2-1 methylation. SNP-based heritability estimates were consistent with the mQTL findings (h2 = 0, 95%CI: -0.14 to 0.14). We found no evidence that age, sex, country of birth, smoking, body mass index, alcohol consumption or diet influenced blood DNA methylation at VTRNA2-1. Genetic factors and adult lifestyle play a minimal role in explaining methylation variability at the heritable VTRNA2-1 cluster.

Rare germline genetic variants and risk of aggressive prostate cancer.

Few genetic risk factors have been demonstrated to be specifically associated with aggressive prostate cancer (PrCa). Here, we report a case-case study of PrCa comparing the prevalence of germline pathogenic/likely pathogenic (P/LP) genetic variants in 787 men with aggressive disease and 769 with nonaggressive disease. Overall, we observed P/LP variants in 11.4% of men with aggressive PrCa and 9.8% of men with nonaggressive PrCa (two-tailed Fisher's exact tests, P = .28). The proportion of BRCA2 and ATM P/LP variant carriers in men with aggressive PrCa exceeded that observed in men with nonaggressive PrCa; 18/787 carriers (2.3%) and 4/769 carriers (0.5%), P = .004, and 14/787 carriers (0.02%) and 5/769 carriers (0.01%), P = .06, respectively. Our findings contribute to the extensive international effort to interpret the genetic variation identified in genes included on gene-panel tests, for which there is currently an insufficient evidence-base for clinical translation in the context of PrCa risk.

Is RNASEL:p.Glu265* a modifier of early-onset breast cancer risk for carriers of high-risk mutations?

BACKGROUND: Breast cancer risk for BRCA1 and BRCA2 pathogenic mutation carriers is modified by risk factors that cluster in families, including genetic modifiers of risk. We considered genetic modifiers of risk for carriers of high-risk mutations in other breast cancer susceptibility genes. METHODS: In a family known to carry the high-risk mutation PALB2:c.3113G>A (p.Trp1038*), whole-exome sequencing was performed on germline DNA from four affected women, three of whom were mutation carriers. RESULTS: RNASEL:p.Glu265* was identified in one of the PALB2 carriers who had two primary invasive breast cancer diagnoses before 50 years. Gene-panel testing of BRCA1, BRCA2, PALB2 and RNASEL in the Australian Breast Cancer Family Registry identified five carriers of RNASEL:p.Glu265* in 591 early onset breast cancer cases. Three of the five women (60%) carrying RNASEL:p.Glu265* also carried a pathogenic mutation in a breast cancer susceptibility gene compared with 30 carriers of pathogenic mutations in the 586 non-carriers of RNASEL:p.Glu265* (5%) (p < 0.002). Taqman genotyping demonstrated that the allele frequency of RNASEL:p.Glu265* was similar in affected and unaffected Australian women, consistent with other populations. CONCLUSION: Our study suggests that RNASEL:p.Glu265* may be a genetic modifier of risk for early-onset breast cancer predisposition in carriers of high-risk mutations. Much larger case-case and case-control studies are warranted to test the association observed in this report.

Mutation screening of PALB2 in clinically ascertained families from the Breast Cancer Family Registry.

Loss-of-function mutations in PALB2 are associated with an increased risk of breast cancer, with recent data showing that female breast cancer risks for PALB2 mutation carriers are comparable in magnitude to those for BRCA2 mutation carriers. This study applied targeted massively parallel sequencing to characterize the mutation spectrum of PALB2 in probands attending breast cancer genetics clinics in the USA. The coding regions and proximal intron-exon junctions of PALB2 were screened in probands not known to carry a mutation in BRCA1 or BCRA2 from 1,250 families enrolled through familial cancer clinics by the Breast Cancer Family Registry. Mutation screening was performed using Hi-Plex, an amplicon-based targeted massively parallel sequencing platform. Screening of PALB2 was successful in 1,240/1,250 probands and identified nine women with protein-truncating mutations (three nonsense mutations and five frameshift mutations). Four of the 33 missense variants were predicted to be deleterious to protein function by in silico analysis using two different programs. Analysis of tumors from carriers of truncating mutations revealed that the majority were high histological grade, invasive ductal carcinomas. Young onset was apparent in most families, with 19 breast cancers under 50 years of age, including eight under the age of 40 years. Our data demonstrate the utility of Hi-Plex in the context of high-throughput testing for rare genetic mutations and provide additional timely information about the nature and prevalence of PALB2 mutations, to enhance risk assessment and risk management of women at high risk of cancer attending clinical genetic services.

Conventional versus implant-retained overlay dentures: a pilot study of masseter and anterior temporalis electromyography.

Implant-supported overlay dentures (ISODs) have been widely accepted among patients using conventional removable complete dentures (CRCDs). The present study aimed to comparatively study conventional and ISODs in terms of function and coordination of masticatory muscles using electromyograms. Included were 10 patients with ISODs (each with 2 implants in the intercanine area). The mean wave range (MWR) and frequency (MWF) of masseter and temporalis were recorded with (ISOD) and without (CRCD) ball attachments while maximum clenching on cotton rolls (cotton roll clenching), maximum intercuspal clenching (clenching), and unilateral gum chewing (chewing) using electromyography. Data were analyzed in SPAW using t-paired for matched groups and independent-sample t tests for unmatched ones. The MWF differences were not statistically significant with or without attachments (P > .05). Without attachments in place, the MWF of both masseter and temporalis muscles significantly decreased when patients clenched on cotton rolls (P = .01 and .02, respectively) and when chewing unilaterally (both P = .01). With attachments present, the right and left temporalis muscles did not show identical mean wave ranges while chewing (P = .01). Without attachments, this disharmony was seen in the left and right masseter muscles (P = .03). The MWR of masseter was higher in men while chewing with attachments (P = .02). Without attachments, the MWR of temporalis was higher in women while cotton roll clenching (P = .03) and chewing (P = .02). These findings are seemingly in favor of improved masticatory function and coordination in edentulous patients with the application of ISODs.

The association of dietary nitrates/nitrites intake and the gut microbial metabolite trimethylamine N-oxide and kynurenine in adults: a population-based study.

Background: Dietary nitrate and nitrite may affect the gut microbiota and its metabolites, such as trimethylamine N-oxide (TMAO) and kynurenine (KYN). However, this association and the exact mechanism are still unclear. Therefore, this study aimed to assess the association between dietary consumption of nitrite and nitrate on TMAO and KYN levels in adults. Methods: This cross-sectional study was employed on a subsample baseline phase of the Tehran University of Medical Sciences (TUMS) Employee's Cohort Study (TEC). A total of 250 adults aged 18 years or older were included in the current analysis. Data on the dietary intakes were collected using a validated dish-based food frequency questionnaire (FFQ), and dietary intakes of nitrite and nitrate were estimated using the FFQ with 144 items. Serum profiles and TMAO and KYN were measured using a standard protocol. Results: The findings of this study demonstrate a significant association between the intake of animal sources of nitrate and nitrite and the likelihood of having elevated levels of TMAO and KYN. Specifically, after adjustment, individuals with the highest intake adherence to nitrates from animal sources exhibited increased odds of having the highest level of TMAO (≥51.02 pg/ml) (OR = 1.51, 95% CI = 0.59-3.88, P = 0.03) and KYN (≥417.41 pg/ml) (OR = 1.75, 95% CI = 0.73-4.17, P = 0.02). Additionally, subjects with the highest animal intake from nitrite sources have 1.73 and 1.45 times higher odds of having the highest levels of TMAO and KYN. These results emphasize the potential implications of animal-derived nitrate and nitrite consumption on the levels of TMAO and KYN. Conclusion: The present evidence indicates that a high level of nitrate and nitrite intake from animal sources can increase the odds of high levels of TMAO and KYN. Further studies suggest that we should better evaluate and understand this association.

Association between DASH and novel atherogenic risk factors, anthropometric indices and foot ulcer indicators in type 2 diabetic patients with foot ulcer: a cross-sectional study.

Purpose: Diabetes can cause nerve damage, vascular issues, and reduced blood flow to organs such as the feet, leading to foot deformities and ulcers due to high glucose levels. A healthy dietary pattern like DASH can improve insulin sensitivity and weight loss. Due to limited data and rare evidence, our study aims to investigate the relationship between DASH diet adherence and anthropometric, cardiovascular, and foot ulcer indicators. Methods: The study included 339 diabetic patients with foot ulcers (122 females and 217 males). The study gathered data on patient dietary intake, anthropometric measurements, biochemistry, foot ulcers, and novel atherogenic risk factors per international definitions. Results: The average BMI of the participants was 29.2 ± 5.0, 28.1 ± 4.3, and 28.2 ± 4.2 in the tertiles of DASH index (P-value: 0.18). By increasing the adherence to the DASH index, the monofilament score did not change significantly OR: 1.47; CI: (0.81-2.67). Also, foot ulcer area did not change significantly between DASH tertiles OR: 1.01; CI: (0.56-1.83). Atherogenic risk factors also decreased among the DASH tertiles, but statistically not significant. Conclusion: DASH adherence did not change neuropathy score and cholindex and cardiovascular risk factors significantly and has no significant effect on foot ulcer size.

Serum levels of trimethylamine N-oxide and kynurenine novel biomarkers are associated with adult metabolic syndrome and its components: a case-control study from the TEC cohort.

Background: Epidemiologic research suggests that gut microbiota alteration (dysbiosis) may play a role in the pathogenesis of metabolic syndrome (MetS). Dysbiosis can influence Trimethylamine N-oxide (TMAO) a gut microbiota-derived metabolite, as well as kynurenine pathways (KP), which are known as a new marker for an early predictor of chronic diseases. Hence, the current study aimed to investigate the association between KYN and TMAO with MetS and its components. Methods: This case-control study was conducted on 250 adults aged 18 years or over of Tehran University of Medical Sciences (TUMS) Employee's Cohort study (TEC) in the baseline phase. Data on the dietary intakes were collected using a validated dish-based food frequency questionnaire (FFQ) and dietary intakes of nitrite and nitrate were estimated using FFQ with 144 items. MetS was defined according to the NCEP ATP criteria. Serum profiles TMAO and KYN were measured by standard protocol. Result: The mean level of TMAO and KYN in subjects with MetS was 51.49 pg/mL and 417.56 nmol/l. High levels of TMAO (≥30.39 pg/mL) with MetS were directly correlated, after adjusting for confounding factors, the odds of MetS in individuals 2.37 times increased (OR: 2.37, 95% CI: 1.31-4.28, P-value = 0.004), also, high levels of KYN (≥297.18 nmol/L) increased odds of Mets+ 1.48 times, which is statistically significant (OR: 1.48, 95% CI: 0.83-2.63, P-value = 0.04). High levels of TMAO compared with the reference group increased the odds of hypertriglyceridemia and low HDL in crude and adjusted models (P < 0.05). Additionally, there was a statistically significant high level of KYN increased odds of abdominal obesity (P < 0.05). Conclusion: Our study revealed a positive association between serum TMAO and KYN levels and MetS and some of its components. For underlying mechanisms and possible clinical implications of the differences. Prospective studies in healthy individuals are necessary.

Association between dietary intakes of Nitrate and Nitrite with Angina and atherogenic index in adults: A cross-sectional study from Tehran University of Medical Sciences employees` cohort (TEC) study.

BACKGROUND: Previous studies have shown that the intake of nitrate and nitrite may be associated with cardiovascular disease. Therefore, this study sought to investigate the association between dietary intakes of nitrate and nitrite with the odds of angina and atherogenic index in adults. METHODS: The study analyzed 1182 adults aged 20+ in the Tehran University of Medical Sciences (TUMS) Employee's Cohort study (TEC), focusing on dietary intakes, angina, and atherogenic indexes, using a validated food frequency questionnaire (FFQ) and the Rose Angina Questionnaire (RAQ). RESULT: The study found a significant inverse relationship between nitrate intake and odds of grade 2 angina. The highest dietary nitrate was associated with 29 % lower odds of grade 1 angina and also, 46 % lower odds of angina possible (P<0.05). Adults with the highest nitrate intake had 29 % lower odds of grade 1 angina and 46 % lower odds of angina possible. Adherence to nitrate reduced CRI, Atherogenic index of plasma, and TyG in participants, but no significant association was found with other factors. CONCLUSION: The study suggests that high nitrate and nitrite intake can alter angina risk, and a reverse association was found between dietary nitrate intake and various atherogenic indices.

Using SNP genotypes to improve the discrimination of a simple breast cancer risk prediction model.

It has been shown that, for women aged 50 years or older, the discriminatory accuracy of the Breast Cancer Risk Prediction Tool (BCRAT) can be modestly improved by the inclusion of information on common single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risk. We aimed to determine whether a similar improvement is seen for earlier onset disease. We used the Australian Breast Cancer Family Registry to study a population-based sample of 962 cases aged 35-59 years, and 463 controls frequency matched for age and for whom genotyping data was available. Overall, the inclusion of data on seven SNPs improved the area under the receiver operating characteristic curve (AUC) from 0.58 (95 % confidence interval [CI] 0.55-0.61) for BCRAT alone to 0.61 (95 % CI 0.58-0.64) for BCRAT and SNP data combined (p < 0.001). For women aged 35-39 years at interview, the corresponding improvement in AUC was from 0.61 (95 % CI 0.56-0.66) to 0.65 (95 % CI 0.60-0.70; p = 0.03), while for women aged 40-49 years at diagnosis, the AUC improved from 0.61 (95 % CI 0.55-0.66) to 0.63 (95 % CI 0.57-0.69; p = 0.04). Using previously used classifications of low, intermediate and high risk, 2.1 % of cases and none of the controls aged 35-39 years, and 10.9 % of cases and 4.0 % of controls aged 40-49 years were classified into a higher risk group. Including information on seven SNPs associated with breast cancer risk, improves the discriminatory accuracy of BCRAT for women aged 35-39 years and 40-49 years. Given, the low absolute risk for women in these age groups, only a small proportion are reclassified into a higher category for predicted 5-year risk of breast cancer.

Cross-platform compatibility of Hi-Plex, a streamlined approach for targeted massively parallel sequencing.

Although per-base sequencing costs have decreased during recent years, library preparation for targeted massively parallel sequencing remains constrained by high reagent cost, limited design flexibility, and protocol complexity. To address these limitations, we previously developed Hi-Plex, a polymerase chain reaction (PCR) massively parallel sequencing strategy for screening panels of genomic target regions. Here, we demonstrate that Hi-Plex applied with hybrid adapters can generate a library suitable for sequencing with both the Ion Torrent and the TruSeq chemistries and that adjusting primer concentrations improves coverage uniformity. These results expand Hi-Plex capabilities as an accurate, affordable, flexible, and rapid approach for various genetic screening applications.

Online positive-oriented counseling, taking vitamin D3 tablet, online lifestyle modification training on premenstrual syndrome: a 3-armed randomized clinical trial.

Lack of absolute treatment for premenstrual syndrome (PMS), its cyclic nature, considerable prevalence (70-90%), and its mental and physical burden imply necessity of effectiveness comparison of various treatments. Although antidepressant and hormonal drugs are well-known medications for PMS, in affected women who can't tolerate, or don't have compatibility or compliance with these drugs, other effective treatments have always been important concern. This study aimed to compare effectiveness of online positive-oriented counseling, taking vitamin D3 tablet, and online lifestyle modification training on alleviating PMS. 3-armed parallel randomized clinical trial was performed on 84 20-40-year-old eligible women with PMS. 84 women were randomly ( www.random.org/sequenc ) allocated into three groups, but data of 77 women (1, n = 25) online positive-oriented counseling group (6 sessions), (2, n = 27) vitamin D3 tablet group (one vitamin D3 tablet weekly for 6 weeks), and (3, n = 25) online lifestyle training group (6 sessions) were analyzed. Vitamin D3 was measured at baseline, week6 and fallow up week10. Primary outcome variable PMS was measured with Premenstrual Symptoms Screening Tool (PSST) at baseline, week 6, and follow-up week 10. Primary outcome satisfaction with intervention method was measured using satisfaction scale at week 6 and follow-up week 10. ANOVA, Repeated Measures, and Paired samples t-test were used for statistical analysis. There was no statistically significant difference in PMS at baseline between three groups respectively (33 ± 5.8, 34.1 ± 7.1, & 35.2 ± 6.4, P = 0.500). However, at follow-up week 10, there was statistically significant difference between three groups (22.3 ± 4.3, 25.4 ± 6.5, & 31.8 ± 6.5; P < 0.001), with greatest improvement in online positive-oriented counseling group (P < 0.001). Satisfaction differed significantly among three groups at week 6 (51 ± 6.8, 46.4 ± 12, & 42.3 ± 6.3, P = 0.001) and follow-up week 10 (55.7 ± 11.6, 51.4 ± 12; & 43 ± 3.3, P < 0.001), with most satisfaction in positive-oriented counseling group (P < 0.001). All three interventions alleviated PMS, but online positive-oriented counseling was more effective and satisfying. Superiority of positive-oriented counseling implies mechanism of adaptation, better relationships, forgiveness, self-mood-regulation, and feasibility of its skills that could be continued individually by women after counseling completion. It is recommended health providers, health policymakers and managers support use of these interventions in treatment program and clinical guidelines.Trial registration: RCT registration number: IRCT20191231045967N1, Registration date:11/02/2020, Registration timing: prospective (IRCT | Survey the effect of vitamin D3 tablet intake, positivism group consulting with changing in life style in the treatment of premenstrual syndrome in women).

The Value of Cytology in the Evaluation of Malignant Pericardial Effusions: A Systematic Review.

Pericardial effusions can be caused by diverse etiologies, including heart-related conditions, kidney failure, trauma, infections, autoimmune diseases, and cancer. This systematic review aimed to assess the role of cytology in identifying the most prevalent cancers related to malignant pericardial effusions (MPEs), the ability of cytology, compared to histology, to detect cancer while evaluating pericardial effusions, and the prognostic impact of MPEs. Four electronic databases were investigated using a predefined algorithm, and specific inclusion and exclusion criteria. We found that the most prevalent primaries associated with MPEs were lung (especially NSCLCs), breast, hematolymphoid, and gastrointestinal cancers. MPEs tended to be hemorrhagic rather than serous or serosanguinous and to occupy larger volumes compared to non-neoplastic effusions. In addition, cytology was shown to exhibit an enhanced ability to detect cancer compared to biopsy in most of the included studies. Lastly, the presence of an MPE was associated with poor prognosis, while survival depended on the specific cancer type detected. Particularly, prognosis was found to be worse when MPEs were caused by lung or gastric cancer, rather than breast or hematolymphoid malignancies. In conclusion, evidence suggests that cytologic evaluation has a significant diagnostic and prognostic impact in patients with MPEs.

Identification of the minimum data set to design a mobile-based application on overweight and obesity management for children and adolescents.

PURPOSE: Designing mobile-based applications is one of the tools to raise the awareness of patients and the care team. Aim of this study is to identify the data elements of a mobile-based application to overweight and obesity management for children and adolescents from the experts' point of view. METHODS: In this descriptive-analytical article, data collection was conducted through library and Internet research. The research population comprised 30 nutritionists selected via simple sampling method. The research instrument was a questionnaire developed by the researcher in four sections: demographic data, assessment data, therapeutic recommendations and application capabilities. Validity and reliability were confirmed by Content Validity Ratio (CVR) and Delphi method respectively. RESULTS: The Minimum Data Set (MDS) required for overweight and obesity management in children and adolescents was designed based on the data from the guidelines of the United States, Canada, Australia, Britain, Iran, and experts' opinions. The importance of this MDS suggested was calculated based on the percentage points given by experts for the demographic data of 100%, the assessment data of 88.33%, the therapeutic recommendations of 97.67%, and the application capabilities of 88.94%. CONCLUSION: Identifying prevention and control minimum data set of overweight and obesity in children and adolescents from the point of view of experts will be effective in improving the applications in this field. This MDS has two parts of data elements: the first for recognition of the framework of evaluating and applying therapeutic methods that can empower parents to manage the child's body mass and the second as a patient's personal record for storage a set of data that can be used by nutritionists in visits to healthcare centers. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-021-00807-1.

Population-Based Estimates of the Age-Specific Cumulative Risk of Breast Cancer for Pathogenic Variants in CHEK2: Findings from the Australian Breast Cancer Family Registry.

Case-control studies of breast cancer have consistently shown that pathogenic variants in CHEK2 are associated with about a 3-fold increased risk of breast cancer. Information about the recurrent protein-truncating variant CHEK2 c.1100delC dominates this estimate. There have been no formal estimates of age-specific cumulative risk of breast cancer for all CHEK2 pathogenic (including likely pathogenic) variants combined. We conducted a population-based case-control-family study of pathogenic CHEK2 variants (26 families, 1071 relatives) and estimated the age-specific cumulative risk of breast cancer using segregation analysis. The estimated hazard ratio for carriers of pathogenic CHEK2 variants (combined) was 4.9 (95% CI 2.5-9.5) relative to non-carriers. The HR for carriers of the CHEK2 c.1100delC variant was estimated to be 3.5 (95% CI 1.02-11.6) and the HR for carriers of all other CHEK2 variants combined was estimated to be 5.7 (95% CI 2.5-12.9). The age-specific cumulative risk of breast cancer was estimated to be 18% (95% CI 11-30%) and 33% (95% CI 21-48%) to age 60 and 80 years, respectively. These findings provide important information for the clinical management of breast cancer risk for women carrying pathogenic variants in CHEK2.

Rare Germline Pathogenic Variants Identified by Multigene Panel Testing and the Risk of Aggressive Prostate Cancer.

While gene panel sequencing is becoming widely used for cancer risk prediction, its clinical utility with respect to predicting aggressive prostate cancer (PrCa) is limited by our current understanding of the genetic risk factors associated with predisposition to this potentially lethal disease phenotype. This study included 837 men diagnosed with aggressive PrCa and 7261 controls (unaffected men and men who did not meet criteria for aggressive PrCa). Rare germline pathogenic variants (including likely pathogenic variants) were identified by targeted sequencing of 26 known or putative cancer predisposition genes. We found that 85 (10%) men with aggressive PrCa and 265 (4%) controls carried a pathogenic variant (p < 0.0001). Aggressive PrCa odds ratios (ORs) were estimated using unconditional logistic regression. Increased risk of aggressive PrCa (OR (95% confidence interval)) was identified for pathogenic variants in BRCA2 (5.8 (2.7-12.4)), BRCA1 (5.5 (1.8-16.6)), and ATM (3.8 (1.6-9.1)). Our study provides further evidence that rare germline pathogenic variants in these genes are associated with increased risk of this aggressive, clinically relevant subset of PrCa. These rare genetic variants could be incorporated into risk prediction models to improve their precision to identify men at highest risk of aggressive prostate cancer and be used to identify men with newly diagnosed prostate cancer who require urgent treatment.

Population-based estimates of breast cancer risk for carriers of pathogenic variants identified by gene-panel testing.

Population-based estimates of breast cancer risk for carriers of pathogenic variants identified by gene-panel testing are urgently required. Most prior research has been based on women selected for high-risk features and more data is needed to make inference about breast cancer risk for women unselected for family history, an important consideration of population screening. We tested 1464 women diagnosed with breast cancer and 862 age-matched controls participating in the Australian Breast Cancer Family Study (ABCFS), and 6549 healthy, older Australian women enroled in the ASPirin in Reducing Events in the Elderly (ASPREE) study for rare germline variants using a 24-gene-panel. Odds ratios (ORs) were estimated using unconditional logistic regression adjusted for age and other potential confounders. We identified pathogenic variants in 11.1% of the ABCFS cases, 3.7% of the ABCFS controls and 2.2% of the ASPREE (control) participants. The estimated breast cancer OR [95% confidence interval] was 5.3 [2.1-16.2] for BRCA1, 4.0 [1.9-9.1] for BRCA2, 3.4 [1.4-8.4] for ATM and 4.3 [1.0-17.0] for PALB2. Our findings provide a population-based perspective to gene-panel testing for breast cancer predisposition and opportunities to improve predictors for identifying women who carry pathogenic variants in breast cancer predisposition genes.

A Medical Decision Support System to Assess Risk Factors for Gastric Cancer Based on Fuzzy Cognitive Map.

Gastric cancer (GC), one of the most common cancers around the world, is a multifactorial disease and there are many risk factors for this disease. Assessing the risk of GC is essential for choosing an appropriate healthcare strategy. There have been very few studies conducted on the development of risk assessment systems for GC. This study is aimed at providing a medical decision support system based on soft computing using fuzzy cognitive maps (FCMs) which will help healthcare professionals to decide on an appropriate individual healthcare strategy based on the risk level of the disease. FCMs are considered as one of the strongest artificial intelligence techniques for complex system modeling. In this system, an FCM based on Nonlinear Hebbian Learning (NHL) algorithm is used. The data used in this study are collected from the medical records of 560 patients referring to Imam Reza Hospital in Tabriz City. 27 effective features in gastric cancer were selected using the opinions of three experts. The prediction accuracy of the proposed method is 95.83%. The results show that the proposed method is more accurate than other decision-making algorithms, such as decision trees, Naïve Bayes, and ANN. From the perspective of healthcare professionals, the proposed medical decision support system is simple, comprehensive, and more effective than previous models for assessing the risk of GC and can help them to predict the risk factors for GC in the clinical setting.