Understanding the anatomy of dermoscopy of melanocytic skin tumours: Correlation in vivo with line-field optical coherence tomography.

BACKGROUND: Early melanoma detection is the main factor affecting prognosis and survival. For that reason, non-invasive technologies have been developed to provide a more accurate diagnosis. Recently, line-field confocal optical coherence tomography (LC-OCT) was developed to provide an in vivo, imaging device, with deep penetration and cellular resolution in three dimensions. Combining the advantages of conventional OCT and reflectance confocal microscopy, this tool seems to be particularly suitable for melanocytic lesions. OBJECTIVES: The objective of this study was to identify and describe the correlation between specific dermoscopic criteria and LC-OCT features in three dimensions associated with melanocytic lesions. METHODS: Dermoscopic and LC-OCT images of 126 melanocytic lesions were acquired in three different centres. The following dermoscopic criteria have been considered: reticular pattern, dots and globules, structureless areas, blue-whitish veil, regression structures, negative network, homogeneous pattern, streaks and blotches. RESULTS: 69 (55%) benign and 57 (45%) malignant lesions were analysed. A regular reticular pattern was found associated in the 75% of the cases with the presence of elongated rete ridges with pigmented cells along the basal layer, while atypical reticular pattern showed an irregular organization of rete ridges with melanocytic hyperplasia, broadened and fused ridges and elongated nests. Both typical and atypical dots and globules were found associated with melanocytic nests in the dermis or at the dermoepidermal junction (DEJ), as well as with keratin cysts/pseudocysts. Grey globules corresponded to the presence of melanin-containing dermal inflammatory cells (melanophages) within the papillae. Structureless brown/black areas correlated with alterations of the DEJ. We observed the same DEJ alterations, but with the presence of dermal melanophages, in 36% of the cases of blue/white/grey structureless areas. A description of each LC-OCT/dermoscopy correlation was made. CONCLUSIONS: LC-OCT permitted for the first time to perform an in vivo, 3D correlation between dermoscopic criteria and pathological-like features of melanocytic lesions.

Quantitative structure-property relationship modelling for predicting retention indices of essential oils based on an improved horse herd optimization algorithm.

The horse herd optimization algorithm (HOA), one of the more contemporary metaheuristic algorithms, has demonstrated superior performance in a number of challenging optimization tasks. In the present work, the descriptor selection issue is resolved by classifying different essential oil retention indices using the binary form, BHOA. Based on internal and external prediction criteria, Z-shape transfer functions (ZTF) were tested to verify their efficiency in improving BHOA performance in QSPR modelling for predicting retention indices of essential oils. The evaluation criteria involved the mean-squared error of the training and testing datasets (MSE), and leave-one-out internal and external validation (Q2). The degree of convergence of the proposed Z-shaped transfer functions was compared. In addition, K-fold cross validation with k = 5 was applied. The results show that ZTF, especially ZTF1, greatly improves the performance of the original BHOA. Comparatively speaking, ZTF, especially ZTF1, exhibits the fastest convergence behaviour of the binary algorithms. It chooses the fewest descriptors and requires the fewest iterations to achieve excellent prediction performance.

QSAR classification model for diverse series of antifungal agents based on binary coyote optimization algorithm.

One of the recently developed metaheuristic algorithms, the coyote optimization algorithm (COA), has shown to perform better in a number of difficult optimization tasks. The binary form, BCOA, is used in this study as a solution to the descriptor selection issue in classifying diverse antifungal series. Z-shape transfer functions (ZTF) are evaluated to verify their efficiency in improving BCOA performance in QSAR classification based on classification accuracy (CA), the geometric mean of sensitivity and specificity (G-mean), and the area under the curve (AUC). The Kruskal-Wallis test is also applied to show the statistical differences between the functions. The efficacy of the best suggested transfer function, ZTF4, is further assessed by comparing it to the most recent binary algorithms. The results prove that ZTF, especially ZTF4, significantly improves the performance of the original BCOA. The ZTF4 function yields the best CA and G-mean of 99.03% and 0.992%, respectively. It shows the fastest convergence behaviour compared to other binary algorithms. It takes the fewest iterations to reach high classification performance and selects the fewest descriptors. In conclusion, the obtained results indicate the ability of the ZTF4-based BCOA to find the smallest subset of descriptors while maintaining the best classification accuracy performance.

An improved opposition-based crow search algorithm for biodegradable material classification.

The development of a reliable quantitative structure-activity relationship (QSAR) classification model with a small number of molecular descriptors is a crucial step in chemometrics. In this study, an improvement of crow search algorithm (CSA) is proposed by adapting the opposite-based learning (OBL) approach, which is named as OBL-CSA, to improve the exploration and exploitation capability of the CSA in quantitative structure-biodegradation relationship (QSBR) modelling of classifying the biodegradable materials. The results reveal that the performance of OBL-CSA not only manifest in improving the classification performance, but also in reduced computational time required to complete the process when compared to the standard CSA and other four optimization algorithms tested, which are the particle swarm algorithm (PSO), black hole algorithm (BHA), grey wolf algorithm (GWA), and whale optimization algorithm (WOA). In conclusion, the OBL-CSA could be a valuable resource in the classification of biodegradable materials.

Quantitative structure-activity relationship model for classifying the diverse series of antifungal agents using ratio weighted penalized logistic regression.

One of the most challenging issues when facing a Quantitative structure-activity relationship (QSAR) classification model is to deal with the descriptor selection. Penalized methods have been adapted and have gained popularity as a key for simultaneously performing descriptor selection and QSAR classification model estimation. However, penalized methods have drawbacks such as having biases and inconsistencies that make they lack the oracle properties. This paper proposes an adaptive penalized logistic regression (APLR) to overcome these drawbacks. This is done by employing a ratio (BWR) of the descriptors between-groups sum of squares (BSS) to the within-groups sum of squares (WSS) for each descriptor as a weight inside the L1-norm. The proposed method was applied to one dataset that consists of a diverse series of antimicrobial agents with their respective bioactivities against Candida albicans. By experimental study, it has been shown that the proposed method (APLR) was more efficient in the selection of descriptors and classification accuracy than the other competitive methods that could be used in developing QSAR classification models. Another dataset was also successfully experienced. Therefore, it can be concluded that the APLR method had significant impact on QSAR analysis and studies.

A QSAR model for predicting antidiabetic activity of dipeptidyl peptidase-IV inhibitors by enhanced binary gravitational search algorithm.

Time-varying binary gravitational search algorithm (TVBGSA) is proposed for predicting antidiabetic activity of 134 dipeptidyl peptidase-IV (DPP-IV) inhibitors. To improve the performance of the binary gravitational search algorithm (BGSA) method, we propose a dynamic time-varying transfer function. A new control parameter, µ , is added in the original transfer function as a time-varying variable. The TVBGSA-based model was internally and externally validated based on Qint2 , QLGO2 , QBoot2 , MSEtrain , Qext2 , MSEtest , Y-randomization test, and applicability domain evaluation. The validation results indicate that the proposed TVBGSA model is robust and not due to chance correlation. The descriptor selection and prediction performance of TVBGSA outperform BGSA method. TVBGSA shows higher Qint2 of 0.957, QLGO2 of 0.951, QBoot2 of 0.954, Qext2 of 0.938, and lower MSEtrain and MSEtest compared to obtained results by BGSA, indicating the best prediction performance of the proposed TVBGSA model. The results clearly reveal that the proposed TVBGSA method is useful for constructing reliable and robust QSARs for predicting antidiabetic activity of DPP-IV inhibitors prior to designing and experimental synthesizing of new DPP-IV inhibitors.

QSAR classification model for diverse series of antifungal agents based on improved binary differential search algorithm.

An improved binary differential search (improved BDS) algorithm is proposed for QSAR classification of diverse series of antimicrobial compounds against Candida albicans inhibitors. The transfer functions is the most important component of the BDS algorithm, and converts continuous values of the donor into discrete values. In this paper, the eight types of transfer functions are investigated to verify their efficiency in improving BDS algorithm performance in QSAR classification. The performance was evaluated using three metrics: classification accuracy (CA), geometric mean of sensitivity and specificity (G-mean), and area under the curve. The Kruskal-Wallis test was also applied to show the statistical differences between the functions. Two functions, S1 and V4, show the best classification achievement, with a slightly better performance of V4 than S1. The V4 function takes the lowest iterations and selects the fewest descriptors. In addition, the V4 function yields the best CA and G-mean of 98.07% and 0.977%, respectively. The results prove that the V4 transfer function significantly improves the performance of the original BDS.

A penalized quantitative structure-property relationship study on melting point of energetic carbocyclic nitroaromatic compounds using adaptive bridge penalty.

A penalized quantitative structure-property relationship (QSPR) model with adaptive bridge penalty for predicting the melting points of 92 energetic carbocyclic nitroaromatic compounds is proposed. To ensure the consistency of the descriptor selection of the proposed penalized adaptive bridge (PBridge), we proposed a ridge estimator ([Formula: see text]) as an initial weight in the adaptive bridge penalty. The Bayesian information criterion was applied to ensure the accurate selection of the tuning parameter ([Formula: see text]). The PBridge based model was internally and externally validated based on [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], the Y-randomization test, [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] and the applicability domain. The validation results indicate that the model is robust and not due to chance correlation. The descriptor selection and prediction performance of PBridge for the training dataset outperforms the other methods used. PBridge shows the highest [Formula: see text] of 0.959, [Formula: see text] of 0.953, [Formula: see text] of 0.949 and [Formula: see text] of 0.959, and the lowest [Formula: see text] and [Formula: see text]. For the test dataset, PBridge shows a higher [Formula: see text] of 0.945 and [Formula: see text] of 0.948, and a lower [Formula: see text] and [Formula: see text], indicating its better prediction performance. The results clearly reveal that the proposed PBridge is useful for constructing reliable and robust QSPRs for predicting melting points prior to synthesizing new organic compounds.

A sparse QSRR model for predicting retention indices of essential oils based on robust screening approach.

A robust screening approach and a sparse quantitative structure-retention relationship (QSRR) model for predicting retention indices (RIs) of 169 constituents of essential oils is proposed. The proposed approach is represented in two steps. First, dimension reduction was performed using the proposed modified robust sure independence screening (MR-SIS) method. Second, prediction of RIs was made using the proposed robust sparse QSRR with smoothly clipped absolute deviation (SCAD) penalty (RSQSRR). The RSQSRR model was internally and externally validated based on [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], Y-randomization test, [Formula: see text], [Formula: see text], and the applicability domain. The validation results indicate that the model is robust and not due to chance correlation. The descriptor selection and prediction performance of the RSQSRR for training dataset outperform the other two used modelling methods. The RSQSRR shows the highest [Formula: see text], [Formula: see text], and [Formula: see text], and the lowest [Formula: see text]. For the test dataset, the RSQSRR shows a high external validation value ([Formula: see text]), and a low value of [Formula: see text] compared with the other methods, indicating its higher predictive ability. In conclusion, the results reveal that the proposed RSQSRR is an efficient approach for modelling high dimensional QSRRs and the method is useful for the estimation of RIs of essential oils that have not been experimentally tested.

High-dimensional QSAR modelling using penalized linear regression model with L1/2-norm.

In high-dimensional quantitative structure-activity relationship (QSAR) modelling, penalization methods have been a popular choice to simultaneously address molecular descriptor selection and QSAR model estimation. In this study, a penalized linear regression model with L1/2-norm is proposed. Furthermore, the local linear approximation algorithm is utilized to avoid the non-convexity of the proposed method. The potential applicability of the proposed method is tested on several benchmark data sets. Compared with other commonly used penalized methods, the proposed method can not only obtain the best predictive ability, but also provide an easily interpretable QSAR model. In addition, it is noteworthy that the results obtained in terms of applicability domain and Y-randomization test provide an efficient and a robust QSAR model. It is evident from the results that the proposed method may possibly be a promising penalized method in the field of computational chemistry research, especially when the number of molecular descriptors exceeds the number of compounds.

Radical radiation vs surgery plus post-operative radiation in advanced (resectable) supraglottic larynx and pyriform sinus cancers: a prospective randomized study.

AIM: Survival in head and neck cancers reflect loco-regional control. With an aim of organ and function preservation the present study was undertaken to compare local failure and survivals. MATERIAL AND METHODS: Between August 1991-December 1995, 72 patients with resectable advanced supraglottic cancers, were randomized to radical surgery followed by post-operative radiation therapy (Sx+PORT) (Arm I) or radical radiation therapy followed by salvage surgery (RRT+/-SSx) (Arm II). RESULTS: Sixty-four of 72 patients were evaluable, 55 were T3 (86%) and 9 were T4 (14%) tumors. In Arm I (n=35) with a mean follow-up of 24 months (2-86 months), 21 patients were alive without disease. Six patients had recurrence, one each at local and tracheostomy stoma, four had nodal recurrence only, and two developed 2nd primary in soft palate/tonsil and parotid at 15 and 18 months respectively. In Arm II (n=29), with a mean follow-up of 24 months (3-81 months), 14 patients were alive without disease. Thirteen patients had recurrence, eight had local (one patient had persistent disease), two nodal only, three loco-regional and two patients developed distant metastasis (lung). One out of eight local recurrence and 2/2 nodal recurrences were salvaged with Sx. There was a significant difference in disease-free survival between the two treatment arms, DFS (5 years) of 70% in Arm I vs 50% in Arm II (p=0.04), but did not have any impact on overall survival OAS (5 years); 73% vs 77% (p=0.79). Voice/laryngeal preservation was possible in 18/29 patients (62%) treated with RRT+/- Sx, without significantly affecting the OAS. "Pathological upstaging" was another significant finding seen in 64% of clinical T3 after radical surgery. CONCLUSION: RRT+/-SSx can be a feasible option in low volume, favourable resectable stage III and IV supraglottic lesions for better quality of life.

Prognostic factors in head and neck soft tissue sarcomas.

BACKGROUND: Soft tissue sarcomas of head and neck constitute a heterogeneous group of rare malignant tumors occurring at rare sites. The purpose of this retrospective study is to evaluate the pathologic features, treatment modalities, outcome, patterns of failure, survival, and other prognostic factors. METHODS: The medical records of 72 patients whose tumors were diagnosed as head and neck sarcomas, treated at Tata Memorial Center between 1981 to 1995 were reviewed. Potential prognostic factors including age, gender, tumor size, histology, grade, and adjuvant treatment were evaluated. RESULTS: The overall and disease free survival at 5 years was 60% and 45%, respectively. The median survival and follow-up was 76 and 38 months, respectively. Thirty-two patients (44.4%) developed recurrence of which 13 patients were salvaged. The univariate and multivariate analysis showed tumor size and grade as important prognostic factors for the survival. CONCLUSIONS: Tumor size greater than 5 cm and high grade tumors were important prognostic factors for survival. Every effort should be made for early diagnosis and wide surgical excision. For localized recurrent tumors without evidence of distant metastasis, surgery should be attempted whenever possible. High rates of locoregional failure in head and neck area indicate the need for improved treatment strategies.

Characterization of tumor-associated antigens on human oral squamous cell carcinomas using monoclonal antibody 3F8E3.

Tumor associated antigen (TAA) on oral squamous cell carcinoma (SCC) was characterized using the monoclonal antibody (MAb) 3F8E3. Flow cytometric analysis revealed a varying degree of reactivity of MAb 3F8E3 to TAA on oral tumor cells. Pretreatment of SCC cells with pronase and trypsin annulled the reactivity of MAb 3F8E3. Sodium metaperiodate (NaIO4) and neuraminidase marginally enhanced the binding of 3F8E3 on oral SCC cells. The studies indicate that the TAA recognized by MAb 3F8E3 on oral tumors is a protein moiety. On Western blotting MAb 3F8E3 showed reactivity to proteins with a molecular weight of 60-66 kDa on oral tumor lysates. MAb 3F8E3 reacted strongly to recombinant human hsp60 and 70 in ELISA. The results suggest that MAb 3F8E3 may react to an epitope expressed on a family of heat shock proteins.

Complications following gastric transposition after total laryngo-pharyngectomy.

AIMS: To investigate restoration of the pharynx after total laryngo-pharyngectomy (TLP), one of the major problems in head and neck surgery. METHODS: A retrospective analysis of 60 patients undergoing total laryngo-pharyngectomy with gastric transposition was performed between June 1991 and June 1996. The analysis focused on morbidity, mortality and long-term function following gastric transposition. RESULTS: The post-operative mortality was 8.3% and the peri-operative morbidity 31.2%. The average hospital stay was 15 days. Immediate restoration of swallowing was achieved in 83% of patients. CONCLUSIONS: Gastric transposition after total laryngo-pharyngectomy is a safe procedure and can be performed with low mortality, acceptable morbidity and good long-term function.

Human gamma delta T cells recognize heat shock protein-60 on oral tumor cells.

In the present investigations, gammadelta T cells were isolated from the peripheral blood of oral cancer patients and analyzed for their immunophenotype and cytotoxic potential. Flow-cytometric analysis revealed a dominant population expressing Vgamma9 and Vdelta2 T-cell receptors. In a 4-hr 51Cr-release assay, activated gammadelta T cells showed specific cytotoxicity against Daudi Burkitt's lymphoma cells and fresh oral tumor cells. Cold target competition assays demonstrated that gammadelta T cells recognize a common ligand on Daudi and oral tumor cells. Expression of heat shock protein 60 (hsp60) molecules was detected on the surface of Daudi as well as oral tumor cells by flow cytometry and immunoprecipitation of surface biotinylated cells by anti-hsp60 monoclonal antibody (MAb). Such MAbs brought about a significant inhibition of cytotoxicity of gammadelta T cells against Daudi and oral tumor cells. The results suggest that gammadelta T cells isolated from the peripheral blood of oral cancer patients have the ability to lyse oral tumor cells. The lysis of oral tumor cells occurs via recognition of hsp60 on the surface of oral tumor cells.

Analysis of DNA ploidy and expression of tumour-associated antigens on human oral carcinomas xenografted in nude mice.

Human squamous cell carcinomas (SCC) of the oral cavity were successfully established as xenografts in nude mice. Tumours with higher malignancy scores and involvement of lymph nodes in patients were more readily accepted as xenografts in nude mice. The xenografted tumours were characterised with respect to morphology, histology, DNA index and expression of tumour-associated antigens (TAA). Flow cytometric analysis of cellular DNA content revealed that many of the xenografts retained the parent tumour DNA pattern while some of the xenografts showed progression to aneuploidy. All the xenografted tumours expressed TAA recognised by monoclonal antibody (MAb) 3F8E3. On Western blotting, MAb 3F8E3 recognised proteins of molecular weight 62-64 kDa on parent and xenografted tumours. In general, the xenografts reflect many of the characteristics of the tumours from which they were derived and may provide a useful model for investigating newer approaches of treatment and diagnosis.

Limiting dilution analysis of proliferating and cytotoxic lymphocytes in the peripheral blood and tumours of oral cancer patients.

Frequencies of proliferating and cytotoxic lymphocytes from the peripheral blood and tumour tissue of oral cancer patients and healthy individuals were monitored using limiting dilution analysis. Significantly lower precursor frequencies of proliferating lymphocytes were observed in the peripheral blood and tumour tissue of oral cancer patients. A high frequency of natural killer (NK) cells but low cytotoxic T lymphocytes (CTL) was observed in the peripheral blood compartment of oral cancer patients as compared to healthy individuals. A marked reduction in both NK and CTL frequencies in the tumour tissue compared to the peripheral blood was observed. In the tumour tissues, increased percentages of activated CD4+ lymphocytes as compared to CD8+ lymphocytes were observed. Our results suggest that impaired proliferative and cytotoxic potential of tumour infiltrating lymphocytes may play an important role in the escape of tumour cells from the immune system.

Perioperative chemotherapy in patients with oral cancer.

In the final report of a prospective, randomized controlled clinical trial, we report the results of using adjuvant perioperative chemotherapy in patients with oral cancer. Our study is based on the hypothesis of Goldie and Coldman. A total of 135 patients with alveolobuccal carcinoma, classified as clinically stage III and IV, were entered on the protocol. After a curative resection, they were randomized. The patients in the test arm of the study received methotrexate 50 mg/m2 on the 3rd, 10th, and 17th postoperative days. The patients in the control arm underwent observation. This analysis at 24 months showed a disease-free survival rate of 61% in the test arm versus 37% in the control arm, which is statistically highly significant (P < 0.01). Analysis of the recurrence pattern showed that recurrence at the primary site was dramatically reduced during the first 6 postoperative months (P = 0.002). Our study provided further clinical evidence in support of the concepts of Goldie and Coldman that the timing of chemotherapeutic drugs is critical for a successful end result.

Laryngopharyngoesophagectomy with gastric pull-up for synchronous primary of vocal cord and oesophagus--a case report & review of literature.

Synchronous primaries in head and neck cancer pose a difficult management problem. A rare case of Synchronous primary of vocal cord and oesophagus was treated at the same sitting by laryngo-pharyngo-oesophagectomy with gastric pull up. We report this case and review the literature in this report.

Craniofacial excision for recurrent osteogenic sarcoma of maxilla.

Two cases of recurrent osteogenic sarcoma of the antro-ethmoidal complex treated at our hospital by a craniofacial resection are presented. The imperative need to treat osteogenic sarcomas of the maxilla primarily by a radical approach such as a craniofacial resection is emphasized.