GenEpi: gene-based epistasis discovery using machine learning.

BackgroundGenome-wide association studies (GWAS) provide a powerful means to identify associations between genetic variants and phenotypes. However, GWAS techniques for detecting epistasis, the interactions between genetic variants associated with phenotypes, are still limited. We believe that developing an efficient and effective GWAS method to detect epistasis will be a key for discovering sophisticated pathogenesis, which is especially important for complex diseases such as Alzheimer's disease (AD).ResultsIn this regard, this study presents GenEpi, a computational package to uncover epistasis associated with phenotypes by the proposed machine learning approach. GenEpi identifies both within-gene and cross-gene epistasis through a two-stage modeling workflow. In both stages, GenEpi adopts two-element combinatorial encoding when producing features and constructs the prediction models by L1-regularized regression with stability selection. The simulated data showed that GenEpi outperforms other widely-used methods on detecting the ground-truth epistasis. As real data is concerned, this study uses AD as an example to reveal the capability of GenEpi in finding disease-related variants and variant interactions that show both biological meanings and predictive power.ConclusionsThe results on simulation data and AD demonstrated that GenEpi has the ability to detect the epistasis associated with phenotypes effectively and efficiently. The released package can be generalized to largely facilitate the studies of many complex diseases in the near future

The nucleolar protein NIFK promotes cancer progression via CK1α/β-catenin in metastasis and Ki-67-dependent cell proliferation.

Nucleolar protein interacting with the FHA domain of pKi-67 (NIFK) is a Ki-67-interacting protein. However, its precise function in cancer remains largely uninvestigated. Here we show the clinical significance and metastatic mechanism of NIFK in lung cancer. NIFK expression is clinically associated with poor prognosis and metastasis. Furthermore, NIFK enhances Ki-67-dependent proliferation, and promotes migration, invasion in vitro and metastasis in vivo via downregulation of casein kinase 1α (CK1α), a suppressor of pro-metastatic TCF4/β-catenin signaling. Inversely, CK1α is upregulated upon NIFK knockdown. The silencing of CK1α expression in NIFK-silenced cells restores TCF4/β-catenin transcriptional activity, cell migration, and metastasis. Furthermore, RUNX1 is identified as a transcription factor of CSNK1A1 (CK1α) that is negatively regulated by NIFK. Our results demonstrate the prognostic value of NIFK, and suggest that NIFK is required for lung cancer progression via the RUNX1-dependent CK1α repression, which activates TCF4/β-catenin signaling in metastasis and the Ki-67-dependent regulation in cell proliferation

Effect of mask coverage on face identification in Taiwanese men and women

Mask wearing is the easiest and most effective way to avoid COVID-19 infection; however, it affects interpersonal activities, especially face identification. This study examined the effects of three mask coverage levels (full coverage, FC; coverage up to the middle [MB] or bottom of the nose bridge [BB]) on face identification accuracy and time. A total of 115 university students (60 men and 55 women) were recruited to conduct a computer-based simulation test consisting of 30 questions (10 questions [five face images each of men and women] for the three mask coverage levels). One unmasked target face and four face images with a specified mask coverage level were designed for each question, and the participants were requested to select the same face from the four covered face images on the basis of the target face. The ANOVA results indicated that identification accuracy was significantly affected by sex (p < 0.01) and the mask coverage level (p < 0.001), whereas identification time was only influenced by sex (p < 0.05). The multiple comparison results indicated that the identification accuracy rate for faces wearing a mask with FC (90.3%) was significantly lower than for those wearing masks with coverage up to the MB (93.7%) and BB (94.9%) positions; however, no difference in identification accuracy rate was observed between the MB and BB levels. Women exhibited a higher identification accuracy rate than men (94.1% vs. 91.9%) in identifying unfamiliar faces, even though they may spend less time identifying the images. A smaller mask coverage level (i.e., the BB level) does not facilitate face identification. The findings can be served as a reference for people to trade-off between wearing a mask and interpersonal interaction in their daily activities

Brief advice and active referral for smoking cessation services among community smokers: a study protocol for randomized controlled trial

Abstract Background Most smokers do not use smoking cessation (SC) services although it increases successful quits. Passive referral providing SC information to smokers is commonly used in SC studies. Little was known about active referral in the community setting. This study aims to motivate community smokers to quit by brief SC advice using a validated AWARD model (Ask, Warn, Advise, Refer and Do-it-again) that adjunct with active referral of smokers to various SC services in Hong Kong. Methods/Design This is a single-blinded, parallel three-armed cluster randomized controlled trial (RCT) with two treatment groups of (1) brief SC advice using the AWARD model, active referral to SC services plus a referral card and a health warning leaflet (active referral group) and (2) brief SC advice using AWARD model and health warning leaflet (brief advice group) and a control group receives general very brief advice with a self-help booklet. A total of 1291 smokers will be recruited from 66 clusters (recruitment sessions) with 22 will be allocated to each of the two intervention and one control groups. SC ambassadors will be trained for delivering the interventions and conducting telephone follow-up. The primary outcomes are self-reported 7-days point prevalence (PP) abstinence at 3 and 6 months follow-up. Intention-to-treat principle and multi-level regressions will be used for data analysis. Discussion This is the first RCT on assessing a model combining brief advice and active referral to SC services among community smokers. The results will inform the practices of SC services and intervention studies. Trial registration NCT02539875 (ClinicalTrials.gov registry; registered retrospectively on 22 July 2015

Bevacizumab Dose Affects the Severity of Adverse Events in Gynecologic Malignancies

In this retrospective study, we investigated adverse events and outcomes in patients treated with bevacizumab for ovarian, fallopian tube, or primary peritoneal cancers at a single hospital. We determined the cumulative incidences of various bevacizumab-related adverse events and the correlation between dose and adverse event incidences. We analyzed data from 154 patients that received 251 rounds of bevacizumab as first-line, first salvage, >2 salvage treatments. Adverse events of any grade were observed in 121 (78.6%) patients; at least one grade 3 or 4 adverse event occurred in 32 (20.8%) patients. The two most common events were proteinuria (38.3%) and hypertension (33.8%). The first-line treatment group displayed significantly higher frequencies of hypertension (52.7% vs. 18.9% vs. 15.5%, p < 0.001), wound complications (9.1% vs. 0% vs. 1.2%, p = 0.010), arthralgia (29.1% vs. 11.3% vs. 8.3%, p = 0.003), and reduced range of joint motion (14.5% vs. 5.7% vs. 3.6%, p = 0.046), compared to those in the first and >2 lines salvage groups, respectively (Kruskal–Wallis test). The cumulative incidences of all grades and grades 3/4 of hypertension cumulative incidence plateaued at around 30% for all grades and 10% for grades 3 and 4, at bevacizumab doses above 8080 and 3510 mg, respectively. The proteinuria cumulative incidence plateaued at around 35% for all grades and 3% for grades 3 and 4, at bevacizumab doses above 11,190 and 4530 mg, respectively. We concluded that, in this realistic clinical population, different kinds and higher cumulative incidences of adverse events were observed compared to those reported in previous clinical trials. Moreover, bevacizumab doses showed cumulative toxicity and plateau effects on hypertension and proteinuria

Reliability of flexible low temperature poly-silicon thin film transistor

This work reports the effect of mechanical stress-induced degradation in flexible low-temperature polycrystalline-silicon thin-film transistors. After 100,000 iterations of channel-width-direction mechanical compression at R=2mm, a significant shift of extracted threshold voltage and an abnormal hump at the subthreshold region were found. Simulation reveals that both the strongest mechanical stress and electrical field takes place at both sides of the channel edge, between the polycrystalline silicon and gate insulator. The gate insulator suffered from a serious mechanical stress and result in a defect generation in the gate insulator. The degradation of the threshold voltage shift and the abnormal hump can be ascribed to the electron trapping in these defects. In addition, this work introduced three methods to reduce the degradation cause by the mechanical stress, including the quality improvement of the gate insulator, organic trench structure and active layer with a wing structure. Please click Additional Files below to see the full abstract

Biomechanical investigation of flexor digitorum tendons in trigger finger patients using sonography

Trigger finger (TF) has generally been ascribed to primary changes in the first annular (A1) pulley. Repeated friction between the A1 pulley and flexor digitorum tendons could result in swelling of soft tissues, and thus it has been speculated that TF affects tendons’ biomechanical behaviors. However, the pathology mechanism related to these behaviors remains unclear. The purposes of this study are to understand (1) the variations in the morphologies of the flexor digitorum profundus (FDP) and flexor digitorum superficialis (FDS) between normal fingers and TFs, (2) the differences in the biomechanical behaviors of the FDP and FDS between normal fingers and TFs in various finger flexion positions, and (3) the effect of various finger positions on the biomechanical behaviors of the FDP and FDS