Image operator learning coupled with CNN classification and its application to staff line removal

Many image transformations can be modeled by image operators that are characterized by pixel-wise local functions defined on a finite support window. In image operator learning, these functions are estimated from training data using machine learning techniques. Input size is usually a critical issue when using learning algorithms, and it limits the size of practicable windows. We propose the use of convolutional neural networks (CNNs) to overcome this limitation. The problem of removing staff-lines in music score images is chosen to evaluate the effects of window and convolutional mask sizes on the learned image operator performance. Results show that the CNN based solution outperforms previous ones obtained using conventional learning algorithms or heuristic algorithms, indicating the potential of CNNs as base classifiers in image operator learning. The implementations will be made available on the TRIOSlib project site.Comment: To appear in ICDAR 201

Clinical Implications of FADD Gene Amplification and Protein Overexpression in Taiwanese Oral Cavity Squamous Cell Carcinomas

<div><p>Amplification of 11q13.3 is a frequent event in human cancers, including head and neck squamous cell carcinoma. This chromosome region contains several genes that are potentially cancer drivers, including <i>FADD</i> (Fas associated via death domain), an apoptotic effector that was previously identified as a novel oncogene in laryngeal/pharyngeal cancer. This study was designed to explore the role of FADD in oral squamous cell carcinomas (OSCCs) samples from Taiwanese patients, by assessing copy number variations (CNVs) and protein expression and the clinical implications of these factors in 339 male OSCCs. The intensity of FADD protein expression, as determined by immunohistochemistry, was strongly correlated with gene copy number amplification, as analyzed using a TaqMan CNV assay. Both FADD gene copy number amplification and high protein expression were significantly associated with lymph node metastasis (<i>P</i> < 0.001). Patients with both FADD copy number amplification and high protein expression had the shortest disease-free survival (DFS; <i>P</i> = 0.074 and <i>P</i> = 0.002) and overall survival (OS; <i>P</i> = 0.011 and <i>P</i> = 0.027). After adjusting for primary tumor status, tumor differentiation, lymph node metastasis and age at diagnosis, DFS was still significantly lower in patients with either copy number amplification or high protein expression (hazard ratio [H.R.] = 1.483; 95% confidence interval [C.I.], 1.044–2.106). In conclusion, our data reveal that FADD gene copy number and protein expression can be considered potential prognostic markers and are closely associated with lymph node metastasis in patients with OSCC in Taiwan.</p></div

Immunohistochemical comparison of FADD expression.

<p>FADD protein expression in three OSCC patients and normal epithelium. (A), Normal epithelium showing weak cytoplasmic and nuclear staining as a reference. (B), Representative staining pattern of FADD 1+. (C), FADD 2+. (D) FADD 3+.</p

Clinical Significance in Oral Cavity Squamous Cell Carcinoma of Pathogenic Somatic Mitochondrial Mutations

<div><p>Somatic mutations affecting the mitochondrial DNA (mtDNA) have been frequently observed in human cancers and proposed as important oncological biomarkers. However, the clinical significance of mtDNA mutations in cancer remains unclear. This study was therefore performed to explore the possible clinical use in assessing oral squamous cell carcinoma (OSCC) of pathogenic mtDNA mutations. The entire mitochondrial genome of 300 OSCC with their matched control DNAs was screened by direct sequencing and criteria were set to define a pathogenic somatic mutation. The patients' <i>TP53</i> R72P genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. The relationships between pathogenic somatic mutations, clinicopathogical features, <i>TP53</i> R72P genotype and clinical prognosis were analyzed. Overall, 645 somatic mtDNA mutations were identified and 91 of these mutations were defined as pathogenic. About one quarter (74/300) of the OSCC tumor samples contained pathogenic mutations. Individuals with the <i>TP53</i> R allele had a higher frequency of pathogenic somatic mutation than those with the PP genotype. Kaplan-Meier analysis indicated that <i>TP53</i> R allele patients with pathogenic somatic mutations demonstrated a significant association with a poorer disease-free survival than other individuals (HR = 1.71; 95% CI, 1.15–2.57; <i>p</i> = 0.009) and this phenomenon still existed after adjusting for mtDNA haplogroup, tumor stage with treatment regimens, differentiation and age at diagnosis (HR = 1.59; 95% CI, 1.06–2.40; <i>p</i> = 0.03). Subgroup analyses showed that this phenomenon was limited to patients who received adjuvant radiotherapy/chemo-radiotherapy after surgery. The results strongly indicated that pathogenic mtDNA mutations are a potential prognostic marker for OSCCs. Furthermore, functional mitochondria may play an active role in cancer development and the patient's response to radiotherapy/chemo-radiotherapy.</p></div

Using SCC Antigen and CRP Levels as Prognostic Biomarkers in Recurrent Oral Cavity Squamous Cell Carcinoma

<div><p>Squamous cell carcinoma antigen (SCC-Ag) and C-reactive protein (CRP) levels have been successfully used to stratify risk groups in primary oral squamous cell carcinoma (OSCC) patients; however, related biomarkers have rarely been investigated in recurrent OSCC. The purpose of the present study was to analyze the relationships of SCC-Ag and CRP levels at the time of recurrence with clinical factors and prognosis. We retrospectively recruited patients with recurrence in a cohort of 534 OSCC patients between March 2001 and July 2013. One hundred patients had recurrence. The serum SCC-Ag and CRP levels were measured at the time of cancer diagnosis, 3 to 6 months after treatment with clinical disease-free, and at the time of recurrence. The SCC-Ag levels were significantly lowered after treatment (paired t-test: p = 0.001) and re-elevated at the time of recurrence (paired t-test: p = 0.027). An SCC-Ag level ≥2.0 ng/ml and a CRP level ≥5.0 mg/L at the time of recurrence were significantly associated with recurrent tumor status (P<0.001), recurrent nodal metastasis (χ² trend test: P = 0.020), distant metastasis (P<0.001), and overall survival (P<0.001). Moreover, the influence of both elevated SCC-Ag and CRP levels on overall survival (P<0.001, H.R. [95% CI]: 5.406 [2.210–13.222]) still existed after adjusting for the recurrent tumor stage and patient age. The present study demonstrates that concurrent high levels of both SCC-Ag and CRP at the diagnosis of recurrence acts as a predictor of recurrent tumor status, recurrent advanced tumor stage, distant metastasis, and survival after the diagnosis of recurrence. This study expands the applicability of these two markers in the risk stratification in recurrent OSCC.</p></div

Multivariate Cox regression model of prognostic covariates in 100 patients with oral cavity squamous cell carcinoma regarding their disease-free and overall survival.

<p>HR, hazard ratio; CI, confidence interval.</p>a<p>stages I and II, ^bstages III, IVa, IVb, and IVc.</p><p>OS, overall survival.</p

Survival curves based on analysis of the Fas-associated death domain (FADD) gene CNA.

<p>(A) Kaplan-Meier curves for disease-free survival (DFS).(B) Kaplan-Meier curves for overall survival (OS).</p

Cox regression analysis of disease-free survival in 300 OSCC patients.

<p>Abbreviations: HR, hazard ratio; CI, confidence interval; RT, radiotherapy; CT, chemotherapy.</p

The Mitochondrial DNA Northeast Asia CZD Haplogroup Is Associated with Good Disease-Free Survival among Male Oral Squamous Cell Carcinoma Patients

<div><p>Reprogramming of energy metabolism in cancer cells has been directly/indirectly linked to mitochondria and mitochondrial functional defects and these changes seem to contribute to the development and progression of cancer. Studies have indicated that mitochondrial DNA haplogroups are associated with risk in relation to various diseases including cancer. However, few studies have examined the effect of haplogroups on cancer prognosis outcome. In order to explore the role of haplogroups on oral squamous cell carcinoma (OSCC) prognosis, the mitochondrial genomes of 300 male OSCC patients were comprehensively analyzed by direct sequencing. They were then haplotyped and grouped into four major geographic haplogroups, namely the East Asia AN, Southeast Asia RBF, East Asia MGE and Northeast Asia CZD groups. The Kaplan-Meier plot analysis indicated that individuals who were members of the CZD haplogroup showed a significant association with better disease-free survival (DFS) than the other three haplogroups and this phenomenon still existed after adjusting for tumor stage, differentiation and age at diagnosis (hazard ratio = 0.55; 95% CI = 0.36–0.84). In addition, an interaction between membership of the RBF haplogroup and radiotherapy/chemo-radiotherapy in DFS was also identified. The results strongly support the hypothesis that an individual’s haplogroup, by defining their genomic background, plays an important role in tumor behavior and mitochondrially-targeted anticancer drugs are promising future therapeutic approaches.</p> </div

Associations between mtDNA geographic haplogroup and OSCC clinicopathological parameters.

<p>Associations between mtDNA geographic haplogroup and OSCC clinicopathological parameters.</p