Cancer organoids Opportunities as well as problems to help precision medicine

In this paper, a method for apnea bradycardia detection in preterm infants is presented based on coupled hidden semi Markov model (CHSMM). CHSMM is a generalization of hidden Markov models (HMM) used for modeling mutual interactions among different observations of a stochastic process through using finite number of hidden states with corresponding resting time. We introduce a new set of equations for CHSMM to be integrated in a detection algorithm. Glycochenodeoxycholic acid research buy The detection algorithm was evaluated on a simulated data to detect a specific dynamic and on a clinical dataset of electrocardiogram signals collected from preterm infants for early detection of apnea bradycardia episodes. For simulated data, the proposed algorithm was able to detect the desired dynamic with sensitivity of 96.67% and specificity of 98.98%. Furthermore, the method detected the apnea bradycardia episodes with 94.87% sensitivity and 96.52% specificity with mean time delay of 0.73 s. The results show that the algorithm based on CHSMM is a robust tool for monitoring of preterm infants in detecting apnea bradycardia episodes. Graphical Abstract Apnea Bradycardia detection using Coupled hidden semi Markov Model from electrocardiography. In this model, a sequence of hidden states is assigned to each observation based on the effects of previous states of all observations.
Genetic polymorphisms play an important role in the development of colorectal cancer (CRC). Functional variants in the epidermal growth factor (EGF), survivin, and Ephrin A1 (EFNA1) genes have been previously reported to play a potential role in susceptibility to CRC, but these polymorphisms have not been well replicated. The aim of this study was to assess the association of the EGF 61A>G, Survivin -31G>C, and EFNA1 -1732G>A polymorphisms with the susceptibility to CRC in an Iranian population.
A total of 148 cases diagnosed with CRC and 160 healthy subjects were recruited. The EGF 61A>G, survivin -31G>C, and EFNA1 -1732G>A polymorphisms were genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.
Our data revealed that the homozygous mutant genotype (CC OR = 2.895, 95% CI = 1.092-7.673, p = 0.033) and mutant allele (C OR = 1.629, 95% CI = 1.152-2.303, p = 0.006) of the survivin -31G>C were associated with an increased risk of CRC in the Iranian population. However, our results failed to show an association between the EGF 61A>G and EFNA1 -1732G>A polymorphisms and CRC risk.
Our results revealed that the survivin -31G>C polymorphism might play an important role in development of CRC in Iranian population. However, no association of EGF 61A>G and EFNA1 -1732G>A polymorphisms with CRC risk was found.
A polymorphisms with CRC risk was found.
Mammography screening encounters may represent ideal opportunities to identify high-risk women for risk-based screening. During mammography appointments, radiology practices evaluate breast density and ascertain known breast cancer risk factors. Our purpose was to evaluate the potential for mammographic screening encounters to identify high-risk women by estimating the (1) proportion of high-risk women who report that they have undergone mammographic screening and the (2) proportion of high-risk women who receive recommendations for breast MRI screening.
Women ages 30-85 without breast cancer histories were included from the 2015 National Health Interview Survey, a nationally representative cross-sectional household survey (response rate 80%). Breast Cancer Risk Assessment Tool was used to determine high-risk (lifetime risk>20%). Among high-risk women, primary outcome was proportion reporting mammography screening, secondary outcome was receipt of a breast MRI recommendation after recent mammogram, accigh-risk women, breast imaging centers should consider determining lifetime breast cancer risk during mammography screening visits.
To use the National Cancer Database to assess treatment patterns in very young women with ductal carcinoma in situ (DCIS) given their propensity for higher risk features and increased risk of recurrence.
We used the NCDB to identify female patients who underwent surgery for a first cancer diagnosis of DCIS within three different age groups ≤30, 31-50, and >50. Demographic information, tumor characteristics, and initial treatment patterns were characterized and compared. Univariable and multivariable logistic regression of individuals with hormone-receptor-positive disease who underwent breast-conserving surgery (BCS) was conducted to assess for group differences in adjuvant endocrine therapy utilization. Survival analysis was conducted via Kaplan-Meier method and Cox regression.
We identified 236,832 patients meeting inclusion criteria. Individuals in the youngest group were more likely to be a minority, had better Charlson-Deyo scores, lived further from their treatment facility, and were less oftenone-receptor-positive DCIS who undergo BCS.
Immunogenomics and earlier, pioneering studies, particularly by Whiteside and colleagues, have indicated a positive role for B-cells in breast cancer, as well as a positive role for gamma-delta T-cells. However, these studies have been completely limited to assessing breast cancer tumor tissue.
Our analyses here has shown that blood-borne T-cell receptor gamma (TRG) chain sequences were associated with greater overall survival, of particular note due to the comparative longevity of primary breast cancer patients, whereby assessments of disease-free, but rarely overall survival parameters are possible. Additional immunogenomics approaches narrowed the overall survival correlations to specific, TRG complementarity determining region-3, amino acid (AA) sequence chemical features, independently of many common, confounding variables in the breast cancer setting, such as estrogen or progesterone receptor status.
These results are discussed in the context of patient age and with regard to potential antigenic targets, based on the chemistry of the TRG CDR3 AA sequences associated with the higher survival rates.
These results are discussed in the context of patient age and with regard to potential antigenic targets, based on the chemistry of the TRG CDR3 AA sequences associated with the higher survival rates.
Chromatin remodeling plays an essential role in regulating transcriptional networks and timing of gene expression. Chromatin remodelers such as SWItch/Sucrose Non-Fermentable (SWI/SNF) harbor many protein components, with the catalytic subunit providing ATPase activity to displace histones along or from the DNA molecules, and associated subunits ensuring tissue specificity and transcriptional or co-transcriptional activities. Mutations in several of the SWI/SNF subunits have been linked to cancer. Here, we investigate betweenSMARCD3/Baf60c expression and hormone-positive (ER+) breast cancer.
The level of SMARCD3 was detected by immunohistochemistry in breast cancer patient samples, and expression levels ofSMARCD1,SMARCD2, andSMARCD3were investigated using publicly available datasets from large cohorts of breast cancer patients. Using molecular biology and microscopy, we interrogated the cellular consequences of lowerSMARCD3expression.
Lower proliferation rates were observed in SMARCD3-depleted cells, which reflects a failure of the cell cycle progression and an increase in endoreplication. In the absence of SMARCD3, p21 accumulates in cells, but does not halt the cell cycle, and DNA damage accumulates and remains unrepaired.
Taken together, our data begin to explain why ER+ breast cancer patients with low-SMARCD3 expressing tumors exhibit reduced survival rates compared to patients expressing normal or higher levels of SMARCD3. SMARCD3 might act as a tumor suppressor through regulation of cell cycle checkpoints and could be a reliable and specific breast cancer prognostic biomarker.
Taken together, our data begin to explain why ER+ breast cancer patients with low-SMARCD3 expressing tumors exhibit reduced survival rates compared to patients expressing normal or higher levels of SMARCD3. SMARCD3 might act as a tumor suppressor through regulation of cell cycle checkpoints and could be a reliable and specific breast cancer prognostic biomarker.
Many surgeons believe that the distance from the external opening to the anal verge (DEOAV) predicts the complexity of a cryptoglandular fistulas-in-ano and, therefore, predicts the need for additional imaging. However, there is no evidence to support this. The primary aim of this study was to determine if DEOAV can predict the complexity of a fistula. Secondary aims were clinical outcome and identification of those patients that might not benefit from preoperative imaging.
All patients having surgery for cryptoglandular fistula-in-ano between January 2014 and December 2016 were evaluated. Preoperative imaging was used to classify fistulas as simple or complex. The DEAOV was measured preoperatively and was divided into categories ≤ 1cm, 1-2cm, or > 2cm. The relationship between the DEOAV and complexity of the fistula was investigated. Clinical outcome was recorded and a group of patients that might not benefit from preoperative imaging was identified.
A total of 103 patients [mf = 6538, median age 47 (range 19-79) years] were included. Magnetic resonance imaging identified 39 simple and 64 complex fistulas. The percentage of simple fistula was 88% in fistulas with DEAOV ≤ 1cm, 48% in DEAOV 1-2cm and 38% in > 2cm. There was a significant difference between the complexity of the fistula and the distance to the anal verge (p < 0.001). The overall healing rate was 88%.
The complexity of perianal fistula depends on the DEAOV. We propose that preoperative imaging should be performed in fistulas with external opening > 1cm from the anal verge.
 1 cm from the anal verge.Page 608, 4 Discussion, right column, second paragraph.Background Erectile dysfunction is associated with old age, some morbidities and the use of certain medications. Objective To identify the treatments and drugs related to worsening sexual activity in patients with erectile dysfunction. Setting Patients diagnosed with erectile dysfunction during 2018. Methods This cross-sectional study of a population database identified all drug prescriptions of patients with erectile dysfunction during 2018. Main outcome measure The identification of other comorbidities and potentially inappropriate drugs that could worsen erectile dysfunction. Results A total of 2999 patients with erectile dysfunction (mean age 59.6 ± 12.1 years) were identified. A total of 88.2% received pharmacological treatment for erectile dysfunction, mainly tadalafil (70.5%). A total of 47.6% of all patients received at least one medication associated with worsening erectile dysfunction, especially hydrochlorothiazide (17.0%), metoprolol (7.9%) and sertraline (6.7%). Residing in Cali (OR 1.86; 95% CI 1.52-22.27) or Bucaramanga (OR 2.23; 95% CI 1.39-33.58), having 3 or more chronic comorbidities (OR 1.52; 95% CI 1.04-2.24) and presenting psychiatric (OR 5.5; 95% CI 3.70-8.17), cardiovascular (OR 3.48; 95% CI 2.79-4.33), genitourinary (OR 1.31; 95% CI 1.05-1.64) pathologies or chronic kidney failure (OR 1.84; 95% CI 1.18-2.21) elevated the probability of receiving these prescriptions. Conclusions The pharmacological treatment of erectile dysfunction was in accordance with the recommendations of clinical practice guidelines, but the high proportion of potentially inappropriate prescriptions makes it necessary to promote educational and pharmacovigilance strategies that improve the prescription habits of physicians involved in caring for this group of patients.