Trends of early-onset colorectal cancer in Singapore: an epidemiological study of a multi-ethnic population.

Background: Colorectal cancer (CRC) incidence and mortality in those aged 50 years and above have decreased over the last 2 decades. However, there is a rising incidence in CRC among individuals under 50 years of age, termed early-onset colorectal cancer (EOCRC). EOCRC patients are more advanced stage at diagnosis and may suffer more psychosocial, emotional and financial distress.

Dietary factors and the risk of lung cancer by epidermal growth factor receptor mutation status and histological subtypes.

Background: Previous studies have reported differential associations of certain dietary factors such as soy consumption by epidermal growth factor receptor mutant ( +) subtype of non-small cell lung cancer (NSCLC). However, whether the other dietary factors including meat, fruits, and vegetables have differential risks on different histological and molecular subtypes of lung cancer remains unclear. Therefore, we conducted a case-control study to evaluate these associations.

Estimation of Preclinical State Onset Age and Sojourn Time for Heavy Smokers in Lung Cancer.

Estimation of the three key parameters: onset age of the preclinical state, sojourn time and screening sensitivity is critical in cancer screening, since all other terms are functions of the three. A novel link function to connect sensitivity with time in the preclinical state and the likelihood method were used in this project; since sensitivity depends on how long one has entered the preclinical state relative to the total sojourn time. Simulations using Markov Chain Monte Carlo and maximum likelihood estimate were carried out to estimate the key parameters for male and female heavy smokers separately in the low-dose computed tomography group of the National Lung Screening Trial.

Association between family history and lung cancer risk among Chinese women in Singapore.

Risk factors of lung cancer unrelated to smoking are not well-studied, especially among women. Family history has been shown to play a role in predisposing individuals to lung cancer, but this relationship has not been investigated in the Southeast Asian population. A total of 1159 women were recruited in a case-control study conducted in public hospitals in Singapore from 2005 to 2008.

Effect of body mass index on inpatient rehabilitation outcome after stroke in a Southeast Asian cohort: a prospective study.

Introduction: We examined the association between admission body mass index (BMI) and discharge rehabilitation functional outcome using the functional independence measure (FIM) in a Southeast Asian cohort of stroke patients during inpatient rehabilitation.

Methods: A prospective, observational cohort study of stroke patients admitted to a single inpatient rehabilitation unit was conducted. Using the World Health Organization Asian standards, BMI was classified as underweight (<18.

Tumor volumes as a predictor of response to the anti-EGFR antibody drug conjugate depatuxizumab mafadotin.

Background: The adverse impact of increasing brain tumor size on the efficacy of antibody-drug conjugates (ADCs) was investigated preclinically then validated with clinical data.

Methods—preclinical Study: The impact of tumor size on ADC tumor delivery and treatment response was evaluated in an -amplified patient-derived glioblastoma (GBM) model following treatment with Depatuxizumab mafadotin (Depatux-M). Biodistribution and imaging studies correlated drug distribution with starting treatment volume and anti-tumor activity.

Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia.

We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA.

Hormonal factors in association with lung cancer among Asian women: A pooled analysis from the International Lung Cancer Consortium.

Two thousand sixty-four lung cancer cases and 5342 controls were evaluated in this International Lung Cancer Consortium (ILCCO) pooled analysis on estrogen-related hormonal factors and lung cancer in Asian women. Random effect of study site and fixed effect of age, smoking status, comprehensive smoking index and family history of lung cancer were adjusted for in the multivariable logistic regression models. We found that late onset of menarche conferred elevated odds of lung cancer with adjusted odds ratio (OR) of 1.

Lung Nodule Malignancy Prediction From Longitudinal CT Scans With Siamese Convolutional Attention Networks.

We propose a convolutional attention-based network that allows for use of pre-trained 2-D convolutional feature extractors and is extendable to multi-time-point classification in a Siamese structure. Our proposed framework is evaluated for single- and multi-time-point classification to explore the value that temporal information, such as nodule growth, adds to malignancy prediction. Our results show that the proposed method outperforms a comparable 3-D network with less than half the parameters on single-time-point classification and further achieves performance gains on multi-time-point classification.

Comparing treatment effects of a convenient vibratory positional device to CPAP in positional OSA: a crossover randomised controlled trial.

Objectives: Up to 77% of patients with obstructive sleep apnoea (OSA) have positional OSA (POSA) but traditional positional therapy (PT) methods have failed as they were poorly tolerated. New convenient vibratory PT devices have been invented but while recent studies suggest high treatment efficacy and adherence, there are no published data comparing these devices directly with continuous positive airway pressure (CPAP). Our objective is to evaluate if a convenient vibratory PT device is non-inferior to CPAP in POSA treatment.

Tuberculosis infection and lung adenocarcinoma: Mendelian randomization and pathway analysis of genome-wide association study data from never-smoking Asian women.

We investigated whether genetic susceptibility to tuberculosis (TB) influences lung adenocarcinoma development among never-smokers using TB genome-wide association study (GWAS) results within the Female Lung Cancer Consortium in Asia. Pathway analysis with the adaptive rank truncated product method was used to assess the association between a TB-related gene-set and lung adenocarcinoma using GWAS data from 5512 lung adenocarcinoma cases and 6277 controls. The gene-set consisted of 31 genes containing known/suggestive associations with genetic variants from previous TB-GWAS.

Glutamatergic Receptors Modulate Normoxic but Not Hypoxic Ventilation and Metabolism in Naked Mole Rats.

Naked mole rats () are among the most hypoxia-tolerant mammals, but their physiological responses to acute and chronic sustained hypoxia (CSH), and the molecular underpinnings of these responses, are poorly understood. In the present study we evaluated the acute hypoxic ventilatory response and the occurrence of ventilatory acclimatization to hypoxia following CSH exposure (8-10 days in 8% O) of naked mole rats. We also investigated the role of excitatory glutamatergic signaling in the control of ventilation and metabolism in these conditions.

3-D Active Contour Segmentation Based on Sparse Linear Combination of Training Shapes (SCoTS).

SCoTS captures a sparse representation of shapes in an input image through a linear span of previously delineated shapes in a training repository. The model updates shape prior over level set iterations and captures variabilities in shapes by a sparse combination of the training data. The level set evolution is therefore driven by a data term as well as a term capturing valid prior shapes.

Winner's Curse Correction and Variable Thresholding Improve Performance of Polygenic Risk Modeling Based on Genome-Wide Association Study Summary-Level Data.

Recent heritability analyses have indicated that genome-wide association studies (GWAS) have the potential to improve genetic risk prediction for complex diseases based on polygenic risk score (PRS), a simple modelling technique that can be implemented using summary-level data from the discovery samples. We herein propose modifications to improve the performance of PRS. We introduce threshold-dependent winner's-curse adjustments for marginal association coefficients that are used to weight the single-nucleotide polymorphisms (SNPs) in PRS.

Association between GWAS-identified lung adenocarcinoma susceptibility loci and EGFR mutations in never-smoking Asian women, and comparison with findings from Western populations.

To evaluate associations by EGFR mutation status for lung adenocarcinoma risk among never-smoking Asian women, we conducted a meta-analysis of 11 loci previously identified in genome-wide association studies (GWAS). Genotyping in an additional 10,780 never-smoking cases and 10,938 never-smoking controls from Asia confirmed associations with eight known single nucleotide polymorphisms (SNPs). Two new signals were observed at genome-wide significance (P < 5 × 10-8), namely, rs7216064 (17q24.

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome.

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events.

Naked mole rats exhibit metabolic but not ventilatory plasticity following chronic sustained hypoxia.

Naked mole rats are among the most hypoxia-tolerant mammals identified and live in chronic hypoxia throughout their lives. The physiological mechanisms underlying this tolerance, however, are poorly understood. Most vertebrates hyperventilate in acute hypoxia and exhibit an enhanced hyperventilation following acclimatization to chronic sustained hypoxia (CSH).

Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types.

Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.

Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients.

Correlation of Computed Tomography Measured Presacral Thickness with Body Mass Index.

Sacral colpopexy is often chosen as a reliable approach that effectively resolves vaginal vault prolapse. Advancements in minimally invasive technology, robotic and laparoscopic surgery, have helped facilitate surgical dissection and operation when performing this procedure. An increased presacral thickness can potentially present a surgical challenge when operating in the presacral space.