Parallelization of logic regression analysis on SNP-SNP interactions of a Crohn’s disease dataset model

SNP-SNP interactions have been recognized to be basically important for understanding genetic causes of complex disease traits. Logic regression is an effective methods for identifying SNP-SNP interactions associated with risk of complex disease. However, identifying SNP-SNP interactions are computationally challenging and may take hours, weeks and months to complete. Although parallel computing is a powerful method to accelerate computing time, it is arduous for users to apply this method to logic regression analyses of SNP-SNP interactions because it requires advanced programming skills to correctly partition and distribute data, control and monitor tasks across multi-core CPUs or several computers, and merge output files. In this paper, we present a novel R-library called SNPInt to automatically speed up analyses of SNP-SNP interactions of genome-wide association (GWA) studies using parallel computing without the advanced programming skills. The Crohn’s disease GWA studies dataset from the Wellcome Trust Case Control Consortium (WTCCC) that includes 4,680 individuals with 500,000 SNPs’ genotypes was analyzed using logic regression on a computer cluster to evaluate SNPInt performance. The results from SNPInt with any number of CPUs are the same as the results from non-parallel approach, and SNPInt library quite accelerated the logic regression analysis. For instance, with two hundred genes and twenty permutation rounds, the computing time was continuously decreased from 7.3 days to only 0.9 day when SNPInt applied eight CPUs. Executing analyses of SNP-SNP interactions using the SNPInt library is an effective way to boost performance, and simplify the parallelization of analyses of SNP-SNP interactions

Crucial Role of Rectoanal Inhibitory Reflex in Emptying Function After Anoplasty in Infants with Anorectal Malformations

Constipation is a common problem after reconstructive surgery for anorectal malformations. The underlying pathophysiology of the constipation in these patients is unclear. The objective of this study was to compare manometric disturbance in infants with and without post-anoplasty constipation. Anorectal manometry studies were performed within 12 months of anoplasty, as a part of the follow-up protocol, in 24 infants aged less than 3 years who had anorectal malformations. The manometric profiles studied were mean resting anal pressure (ArP), mean resting rectal pressure (RrP), mean resting rectoanal pressure gradient (RRPG), peak squeeze pressure (PSP), and the presence of the rectoanal inhibitory reflex (RAIR). Eight of 24 infants (33%) experienced constipation during the examination period. There was no difference in pressure profiles between low and non-low anomalies. In the non-constipation group, RrP was 5.1 mmHg, ArP was 21.0 mmHg, RRPG was 16.0 mmHg, and PSP was 88.4 mmHg. In the constipation group, RrP was 7.3 mmHg (p = 0.37), ArP was 37.5 mmHg (p = 0.03), RRPG was 3.05 mmHg (p = 0.05), and PSP was 81.7 mmHg (p = 0.77). RAIR was present in 93.75% of cases without constipation and 12.5% of cases with constipation (p < 0.01). One patient who had clinical conversion from constipation to a good result also showed positive conversion of the RAIR. RAIR and anal resting tone play important roles in emptying function. As far as possible, these functions should be preserved during reconstruction

Factors determining low anterior resection syndrome after rectal cancer resection: A study in Thai patients

Defective defecation function, also known as low anterior resection syndrome (LARS), is a common problem after surgical treatment of rectal cancer that has a detrimental effect on quality of life. This study aimed to look for the incidence of LARS in patients whose native rectum could not be kept and determine factors influencing major LARS. Rectal cancer patients who underwent tumor removal with mesorectal excision and colorectal anastomosis by a colorectal surgeon during the years 2004–2013 were asked to participate a structured interview using the verified version of the Low Anterior Resection Score questionnaire. Clinical parameters were analyzed against the incidence of major LARS. The cut-off anastomotic level that corresponded to the risk of major LARS was calculated by using a receiver operating characteristic curve. Anorectal physiology was compared between those with major LARS and those without LARS by anorectal manometry. This study included 129 patients (67 men and 62 women). Incidences of minor LARS (LAR score 21–29) and major LARS (LARS score ≥ 30) score 21een those with major LARS and those univariate analysis, factors associated with major LARS were extent of operation, presence of temporary ostomy, and chemoradiation therapy. Major LARS was found at 28.2% in those who underwent low anterior resection, which was significantly higher than the incidence of 5.2% in the anterior resection group (p < 0.01). Radiation therapy was the only factor independently associated with major LARS at an odds ratio of 6.55 (95% confidence interval: 2.37–18.15). The receiver operating characteristic curve plot between sensitivity and specificity of the anastomotic level in determining major LARS showed an area under the curve of 0.73. The cut-off anastomotic level that best predicted major LARS was at 5 cm, which gave a negative predictive value of 89%. Individual defecation symptoms that were significantly associated with major LARS included pain on defecation, difficulty holding stool, and needing to use a pad. Anorectal manometry showed a significant difference in the resting anal pressure and squeeze pressure, which suggests that derangement in sphincteric function caused by surgery and postoperative adjuvant treatment may contribute to the LARS. LARS is a significant problem found in about one third of rectal cancer patients after colorectal anastomosis. Symptoms of concern include pain on defecation and decreased ability to hold. Risk of having major LARS increases with adjuvant treatment and lower anastomotic level

The Effect of Phototherapy on Cancer Predisposition Genes of Diabetic and Normal Human Skin Fibroblasts

The purpose of this study was to investigate whether LED light at different wavelengths affects the expression profile of 143 cancer predisposition genes in both diabetic and normal human fibroblasts. In this study, both diabetic and normal fibroblast cell lines were cultured and irradiated with red (635 nm), green (520 nm), and blue (465 nm) LED light for 10 minutes at 0.67 J/cm2 each. After that, mRNA from all cell lines was extracted for microarray analysis. We found that green light activates EPHB2, KIT, ANTXR2, ESCO2, MSR1, EXT1, TSC1, KIT, NF1, BUB1B, FANCD2, EPCAM, FANCD2, NF, DIS3L2, and RET in normal fibroblast cells, while blue and red light can upregulate RUNX1, PDGFRA, EHBP1, GPC3, AXIN2, KDR, GLMN, MSMB, EPHB2, MSR1, KIT, FANCD2, BMPR1A, BUB1B, PDE11A, and RET. Therefore, genetic screening before phototherapy treatment may be required

Molecular Landscape for Malignant Transformation in Diffuse Astrocytoma

Background Malignant transformation (MT) of low-grade gliomas changes dramatically the natural history to poor prognosis. Currently, factors associated with MT of gliomas have been inconclusive, in particular, diffuse astrocytoma (DA). Objective The present study aimed to explore the molecular abnormalities related to MT in the same patients with different MT stages. Methods Twelve specimens from five DA patients with MT were genotyped using next-generation sequencing (NGS) to identify somatic variants in different stages of MT. We used cross-tabulated categorical biological variables and compared the mean of continuous variables to assess for association with MT. Results Ten samples succussed to perform NGS from one male and four females, with ages ranging from 28 to 58 years. The extent of resection was commonly a partial resection following postoperative temozolomide with radiotherapy in 25% of cases. For molecular findings, poly-T-nucleotide insertion in isocitrate dehydrogenase 1 (IDH1) was significantly related to MT as a dose–response relationship (Mann–Whitney's U test, p = 0.02). Also, mutations of KMT2C and GGT1 were frequently found in the present cohort, but those did not significantly differ between the two groups using Fisher's exact test. Conclusion In summary, we identified a novel relationship between poly-T insertion polymorphisms that established the pathogenesis of MT in DA. A further study should be performed to confirm the molecular alteration with more patients

Molecular Subtyping in Muscle-Invasive Bladder Cancer on Predicting Survival and Response of Treatment

Molecular classifications for urothelial bladder cancer appear to be promising in disease prognostication and prediction. This study investigated the novel molecular subtypes of muscle invasive bladder cancer (MIBC). Tumor samples and normal tissues of MIBC patients were submitted for transcriptome sequencing. Expression profiles were clustered using K-means clustering and principal component analysis. The molecular subtypes were also applied to The Cancer Genome Atlas (TCGA) dataset and analyzed for clinical outcome correlation. Three molecular subtypes of MIBC were discovered, clusters A, B, and C. The most differentially upregulated genes in cluster A were BDKRB1, EDNRA, AVPR1A, PDGFRB, and TNC, while the most upregulated genes in cluster C were collagen-related genes, PDGFRB, and PRKG1. For cluster B, COL6A3, COL1A2, COL6A2, tenascin C, and fibroblast growth factor 2 were statistically suppressed. When the centroids of clustering on PCA were applied to TCGA data, the clustering significantly predicted survival outcomes. Cluster B had the best overall survival (OS), and cluster C was associated with poor OS but exhibited the best response to perioperative chemotherapy. Among all groups, cluster B had a better pathologic response to neoadjuvant chemotherapy (40%). Based on the results of the present study, the novel clusters of subtype MIBC appear potentially suitable for integration into clinical practice

Factors determining low anterior resection syndrome after rectal cancer resection: A study in Thai patients

Background/Objective: Defective defecation function, also known as low anterior resection syndrome (LARS), is a common problem after surgical treatment of rectal cancer that has a detrimental effect on quality of life. This study aimed to look for the incidence of LARS in patients whose native rectum could not be kept and determine factors influencing major LARS. Methods: Rectal cancer patients who underwent tumor removal with mesorectal excision and colorectal anastomosis by a colorectal surgeon during the years 2004–2013 were asked to participate a structured interview using the verified version of the Low Anterior Resection Score questionnaire. Clinical parameters were analyzed against the incidence of major LARS. The cut-off anastomotic level that corresponded to the risk of major LARS was calculated by using a receiver operating characteristic curve. Anorectal physiology was compared between those with major LARS and those without LARS by anorectal manometry. Results: This study included 129 patients (67 men and 62 women). Incidences of minor LARS (LAR score 21–29) and major LARS (LARS score ≥ 30) score 21een those with major LARS and those univariate analysis, factors associated with major LARS were extent of operation, presence of temporary ostomy, and chemoradiation therapy. Major LARS was found at 28.2% in those who underwent low anterior resection, which was significantly higher than the incidence of 5.2% in the anterior resection group (p < 0.01). Radiation therapy was the only factor independently associated with major LARS at an odds ratio of 6.55 (95% confidence interval: 2.37–18.15). The receiver operating characteristic curve plot between sensitivity and specificity of the anastomotic level in determining major LARS showed an area under the curve of 0.73. The cut-off anastomotic level that best predicted major LARS was at 5 cm, which gave a negative predictive value of 89%. Individual defecation symptoms that were significantly associated with major LARS included pain on defecation, difficulty holding stool, and needing to use a pad. Anorectal manometry showed a significant difference in the resting anal pressure and squeeze pressure, which suggests that derangement in sphincteric function caused by surgery and postoperative adjuvant treatment may contribute to the LARS. Conclusion: LARS is a significant problem found in about one third of rectal cancer patients after colorectal anastomosis. Symptoms of concern include pain on defecation and decreased ability to hold. Risk of having major LARS increases with adjuvant treatment and lower anastomotic level

An Appraisal of Totally Implantable Venous Access Devices in Pediatric Cancers

Objective: To appraise the experience of a pediatric cancer center in Thailand regarding employment of totally implantable venous access devices (TIVAD). Methods: The records of consecutive patients aged less than 15 years diagnosed malignancy and underwent an implantation from the years 2010 to 2018 were reviewed with the main focus on effective duration and complications of the device. Changes in our practice in perioperative care were also reviewed. Results: A total of 150 lines in 144 patients (103 hematologic malignancies and 41 solid tumors) were included with average age 6.4 years. Neck vein access was used in 62 lines, subclavian vein access in 88 lines. The median follow-up period was 973 days. Immediate complications occurred in 13 cases (9.4%). Excluding cases with death from unrelated causes, the overall TIVAD survival was 985.1 days while event-free device survival was 797.6 days. In cases of hematologic malignancies, which were the main users, 1000-day overall survival and event-free survival of TIVAD were 83.7% and 78.2%, respectively. Catheter-related infections and mechanical obstruction were the 2 most prevalent problems, occurring in 0.20 and 0.08 events/1,000 catheter days, respectively. Infection occurred in 23 patients and gram-negative bacilli were most common. Moreover, subclavian access was significantly related with infectious complications when compared to the neck vein approach. Conclusion: A TIVAD can be used for chemotherapy longer than 3 years without serious complications. Refinement of surgical techniques and improving care process may improve the longevity of the line