Irregular Architecture Research Articles

Influence of structural features in the performance of bioceramic-based composite scaffolds for bone engineering applications: A prediction study

Despite recent years' remarkable progress in medical procedures for bone reconstruction, the implementation of newly developed biomedical materials is still facing technical drawbacks, such as, lack of mechanical strength, impaired cellular proliferation and differentiation, limited osteogenesis and issues related to bone infection, osseointegration and vascularization in large defects.This paper presents a methodology to predict the potential behaviour of bioceramic-based composite scaffolds for bone engineering applications, based on the evaluation of its morphological features, mechanical properties, and mechanical stimulus' input to cells. Chitosan/biphasic calcium phosphates (CH/BCP) composite scaffolds with different structural parameters, namely pore size, filament thickness and layer overlapping, pore size gradient and irregularity on the filament positioning were considered. The finite element simulation was validated against experimental results on 3D printed scaffolds, being proposed an in silico model for the characterization of the scaffolds' material composition. With this study, the influence of the CH/BCP bulk material mechanical properties on the scaffolds mechanical behaviour was demonstrated. CH/BCP show to behave according to a Yeoh hyperelastic material model. Scaffolds with a regular structure and 500 μm filament distance (PL500) or irregular architecture models (IS2 scaffold) demonstrated better equilibrium among the analysed features, namely to promote cell adhesion and migration, nutrient and oxygen flow, vascularization, mechanical capacity to support the load without experiencing premature failure and initial bone formation through the transmission of bone growth mechanical stimulus. A good correlation between this study and literature data was obtained, which highlighted the suitability of the proposed methodology to infer on the scaffold biomechanical behaviour and allowing the scaffold improvement at an early stage of conceptualization.

A Practical and Economical Ultra-wideband Base Station Placement Approach for Indoor Autonomous Driving Systems

Automated valet parking (AVP) has attracted much attention as the entry point to autonomous driving. In an indoor environment, high-precision positioning systems are essential for AVP. Ultra-wideband (UWB) is one of the most widely adopted techniques. However, the base station placement significantly influences the system’s positioning accuracy, especially for the irregular architecture of underground parking lots. This article proposes a three-stage practical and economical layout planning approach for UWB base stations, including determining the deployment strategy and layout parameters and comprehensive adjustment and scheme verification. The approach considers regional differentiation accuracy requirements for AVP, such as ramp area, surface fluctuation area, and narrow area. The adopted positioning method of a UWB system is the time difference of arrival (TDOA), and the evaluation index of positioning accuracy is the horizontal dilution of precision (HDOP). Through experimental tests in an actual parking lot, the proposed approach is confirmed to ensure stability and economy with fewer UWB base stations and can meet the positioning accuracy requirements of AVP.

Enlarging melanocytic lesions with peripheral globular pattern: a dermoscopy and confocal microscopy study.

BACKGROUND Enlarging melanocytic lesions with peripheral globular pattern (EMLPGP) are a pitfall in dermoscopy. Our aim was to evaluate the meaning of EMLPGP and to assess the use of dermoscopy and reflectance confocal microscopy (RCM) in order to improve the clinical management of this subtype of melanocytic lesions. METHODS A total of 135 EMLPGP were recruited and, accordingly to the dermoscopy features, were removed; later, an expert dermoscopist reviewed the lesions blinded to histology. Moreover, a subgroup of 63 lesions who underwent also to RCM, were reviewed by an expert confocalist. RESULTS Patients had a median age of 41 years old and a female prevalence (61.5%). The main anatomic site was the trunk (86%). Histology of the 135 excised EMLPGP disclosed 116 nevi (86%; P<0.0001) and 19 melanomas (14%). On dermoscopy, statistical significance was detected for small globules that were observed in 106 cases (78.5%; P<0.0001), while globules distribution and color did not impact the diagnosis prediction, as well as age, sex or any other patient profile. Considering the RCM, atypical cytology and irregular architecture were detected in 100% of melanomas (P<0.0001). CONCLUSIONS Our study shows that EMLPGPs are detectable in every age and can be a pitfall in especially in high risk patients with an over-excision of lesions. The presence of peripheral globules should be evaluated considering the overall dermoscopic features. RCM can contribute significantly in the management of lesions trough the detection of cyto-architectural atypia. Therefore, RCM in combination with dermoscopy can optimize the reduction of harmless lesions.

Intraductal Papillary Neoplasm of Bile Duct: Updated Clinicopathological Characteristics and Molecular and Genetic Alterations

Intraductal papillary neoplasm of the bile duct (IPNB), a pre-invasive neoplasm of the bile duct, is being established pathologically as a precursor lesion of invasive cholangiocarcinoma (CCA), and at the time of surgical resection, approximately half of IPNBs show stromal invasion (IPNB associated with invasive carcinoma). IPNB can involve any part of the biliary tree. IPNB shows grossly visible, exophytic growth in a dilated bile duct lumen, with histologically villous/papillary neoplastic epithelia with tubular components covering fine fibrovascular stalks. Interestingly, IPNB can be classified into four subtypes (intestinal, gastric, pancreatobiliary and oncocytic), similar to intraductal papillary mucinous neoplasm of the pancreas (IPMN). IPNBs are classified into low-grade and high-grade based on lining epithelial features. The new subclassification of IPNB into types 1 (low-grade dysplasia and high-grade dysplasia with regular architecture) and 2 (high-grade dysplasia with irregular architecture) proposed by the Japan–Korea pathologist group may be useful in the clinical field. The outcome of post-operative IPNBs is more favorable in type 1 than type 2. Recent genetic studies using next-generation sequencing have demonstrated the existence of several groups of mutations of genes: (i) IPNB showing mutations in KRAS, GNAS and RNF43 belonged to type 1, particularly the intestinal subtype, similar to the mutation patterns of IPMN; (ii) IPNB showing mutations in CTNNB1 and lacking mutations in KRAS, GNAS and RNF43 belonged to the pancreatobiliary subtype but differed from IPMN. IPNB showing mutation of TP53, SMAD4 and PIK3CA might reflect complicated and other features characterizing type 2. The recent recognition of IPNBs may facilitate further clinical and basic studies of CCA with respect to the pre-invasive and early invasive stages.

3d phase-contrast nanotomography of unstained human skin biopsies may identify morphological differences in the dermis and epidermis between subjects.

BackgroundEnteric neuropathy is described in most patients with gastrointestinal dysmotility and may be found together with reduced intraepidermal nerve fiber density (IENFD). The aim of this pilot study was to assess whether three‐dimensional (3d) imaging of skin biopsies could be used to examine various tissue components in patients with gastrointestinal dysmotility.Material and methodsFour dysmotility patients of different etiology and two healthy volunteers were included. From each subject, two 3‐mm punch skin biopsies were stained with antibodies against protein gene product 9.5 or evaluated as a whole with two X‐ray phase‐contrast computed tomography (CT) setups, a laboratory µCT setup and a dedicated synchrotron radiation nanoCT end‐station.ResultsTwo patients had reduced IENFD, and two normal IENFD, compared with controls. µCT and X‐ray phase‐contrast holographic nanotomography scanned whole tissue specimens, with optional high‐resolution scans revealing delicate structures, without differentiation of various fibers and cells. Irregular architecture of dermal fibers was observed in the patient with Ehlers‐Danlos syndrome and the patient with idiopathic dysmotility showed an abundance of mesenchymal ground substance.Conclusions3d phase‐contrast tomographic imaging may be useful to illustrate traits of connective tissue dysfunction in various organs and to demonstrate whether disorganized dermal fibers could explain organ dysfunction.

Mucinous Adenomyomatous Pulmonary Hamartoma: Clinicopathologic, Immunohistochemical, and Molecular Features of 6 Cases.

Pulmonary hamartoma (PH) may show various combinations of mesenchymal tissues with entrapment of respiratory epithelium. An uncommon variant of PH prevalently consisting of smooth muscle with mucinous proliferation has been reported in literature under several definitions as sporadic reports. We collected a series of 6 leiomyomatous PH associated with mucinous growth from consultation files (3 cases) and multicentric revision of archival files among 128 consecutive surgically resected PH. The lesions have a prevalence for male gender (5:1) and lower lobes (5:1), with a mean age at diagnosis of 61 years. All cases were incidentally disclosed in asymptomatic patients and had an indolent behavior. At histology, 2 cases consisted uniquely of smooth muscle and 4 also showed mature adipose tissue. The mucinous proliferation consisted of a monotonous growth of columnar cells lacking p63-positive basal cells and expressing pan-CKs, MUC5A, and CK7, but negative with TTF-1, napsin, MUC1, MUC2, MUC6, CK20, and CDX2. Smooth muscle was negative with hormonal receptors. Molecular analysis using a multiplex gene panel did not reveal gene mutations, while ALK, BRAF, and ROS1 were negative. In conclusion, we describe a small series of uncommon PH with prevalent leiomyomatous mesenchymal component associated with a mucinous growth (mucinous adenomyomatous hamartoma). Despite the lack of basal cells coating mucinous proliferation and irregular architecture, the favorable outcome and lack of molecular alterations most likely lay for a benign/low-grade tumor. Pathologists should be aware of this unusual occurrence to prevent a diagnosis of overt malignancy, particularly in frozen section, small biopsy, and cytology.

Разработка компиляторов предметно-ориентированных языков для спецпроцессоров

Specialized processors programmable in domain-specific languages are increasingly used in modern computing systems. The compiler-in-the-loop approach, based on the joint development of a specialized processor and a compiler, is gaining popularity. At the same time, the traditional tools, like GCC and LLVM, are insufficient for the agile development of optimizing compilers that generate target code of an exotic, irregular architecture with static parallelism of operations. The article proposes methods from the field of program synthesis for the implementation of machine-dependent compilation phases. The phases are based on a reduction to SMT problem which allows to get rid of heuristic and approximate approaches, that requires complex software implementation of a compiler. In particular, a synthesis of machine-dependent optimization rules, instruction selection and instruction scheduling combined with register allocation are implemented with help of SMT solver. Practical applications of the developed methods and algorithms are illustrated by the example of a compiler for a specialized processor with an instruction set that accelerates the implementation of lightweight cryptography algorithms in the Internet of Things. The results of compilation and simulation of 8 cryptographic primitives for 3 variants of specialized processor (CISC-like, VLIW-like and a variant with delayed load instruction) show the vitality of the proposed approach.

Solitary fibrous tumor/hemangiopericytoma of the penis.

Solitary fibrous tumor/hemangiopericytoma (SFT-HMP) is a rare spindle-cell mesenchymal tumor, thought to be of myofibroblastic origin. Penile SFT-HMP was mentioned in the literature in two separate case reports which were published in 2015 and 2017. We present the first case of SFT-HMP which is localized on corpus cavernosum of the penis. A 55-year-old man presented to our clinic with a small and gradually growing lesion on his penis for the past year, which recently caused difficulties during sexual intercourse. On physical examination; a well-shaped, nodular non-fluctuant, solid, painless mass, measuring 4×4 cm was palpated. Magnetic resonance imaging showed 5×5 cm mass located on the right corpus cavernosa. Under spinal anesthesia, surgical excision was performed. Pathologically, the tumor had an irregular architecture patterns and was characterized by hypercellular areas separated by thin-walled, branching vessels, lined with a single layer of flattened endothelial cells. SFT-HMP rarely occurs in genital tract and penile presentation is among the rarest. It should be classified and considered under penile masses, especially if the mass is well circumscribed, painless and slowly growing in nature. After differential diagnosis, surgical excision is mandatory.

Enlarging melanocytic lesions with peripheral globular pattern: a dermoscopic and confocal microscopy study.

Enlarging melanocytic lesions with peripheral globular pattern (EMLPGP) are a pitfall in dermoscopy. Our aim was to evaluate the meaning of EMLPGP and to assess the use of dermoscopy and reflectance confocal microscopy (RCM) in order to improve the clinical management of this subtype of melanocytic lesions. A total of 135 EMLPGP were recruited and, accordingly to the dermoscopy features, were removed; later, an expert dermoscopist reviewed the lesions blinded to histology. Moreover, a subgroup of 63 lesions who underwent also to RCM, were reviewed by an expert confocalist. Patients had a median age of 41 years old and a female prevalence (61.5%). The main anatomic site was the trunk (86%). Histology of the 135 excised EMLPGP disclosed 116 nevi (86%; P<0.0001) and 19 melanomas (14%). On dermoscopy, statistical significance was detected for small globules that were observed in 106 cases (78.5%; P<0.0001), while globules distribution and color did not impact the diagnosis prediction, as well as age, sex or any other patient profile. Considering the RCM, atypical cytology and irregular architecture were detected in 100% of melanomas (P<0.0001). Our study shows that EMLPGPs are detectable in every age and can be a pitfall in especially in high risk patients with an over-excision of lesions. The presence of peripheral globules should be evaluated considering the overall dermoscopic features. RCM can contribute significantly in the management of lesions trough the detection of cyto-architectural atypia. Therefore, RCM in combination with dermoscopy can optimize the reduction of harmless lesions.

Capacity Analysis of a Full Duplex Device-to-Device Wireless Network using Voronoi diagrams and Distance Distributions

Full duplex (FD) and Device-to-Device (D2D) communication are two revolutionary protocols that have enabled better spectrum utilization and more reliable data delivery in wireless networks. In addition, stochastic geometry tools have become necessary to characterize the randomness in the present networks with respect to the irregular architecture and the competing access schemes. This work analyses the performance of a mobile network comprising nodes which are randomly distributed in a square area, which are equipped with FD radios, and can communicate using D2D. The base station (BS) nodes and user nodes in the network are modelled as points of a homogenous binomial point process (BPP) and a homogeneous Poisson point process (PPP) respectively. The network area is tessellated into cells using Voronoi diagrams which approximates to a nearest BS-to-user node association policy. The user nodes can cache popular file objects which are available in a centralized server in the network and other nodes in proximity can request for such objects and receive them using D2D. Using well known distance distribution expressions and stochastic geometry analysis, the distribution of the signal-to-interference ratio (SIR), the D2D and FD collaboration probabilities and the average coverage probability are derived. It is shown that a network-wide quality of service is maintained without additional spectrum utilization when the user nodes can be intelligently tuned to transmit and receive using FD and/or D2D modes. Keywords— Device-to-Device Communication, Full Duplex Communication, stochastic geometry analysis, Voronoi diagrams, Distance Distributions

Atomic Force Microscopy of Side Wall and Septa Peptidoglycan From Bacillus subtilis Reveals an Architectural Remodeling During Growth.

Peptidoglycan is the fundamental structural constituent of the bacterial cell wall. Despite many years of research, the architecture of peptidoglycan is still largely elusive. Here, we report the high-resolution architecture of peptidoglycan from the model Gram-positive bacterium Bacillus subtilis. We provide high-resolution evidence of peptidoglycan architecture remodeling at different growth stages. Side wall peptidoglycan from B. subtilis strain AS1.398 changed from an irregular architecture in exponential growth phase to an ordered cable-like architecture in stationary phase. Thickness of side wall peptidoglycan was found to be related with growth stages, with a slight increase after transition to stationary phase. Septal disks were synthesized progressively toward the center, while the surface features were less clear than those imaged with side walls. Compared with previous studies, our results revealed slight differences in architecture of peptidoglycan from different B. subtilis strains, expanding our knowledge about the architectural features of B. subtilis peptidoglycan.

Computational Simulation of Tumor Hypoxia Based on In Vivo Microvasculature Assessed in a Dorsal Skin Window Chamber.

Malignant growth usually leads to the depletion of oxygen (O2) supply in most solid tumors. Hypoxia can cause resistance to standard radiotherapy, some chemotherapy and immunotherapy. Furthermore, it can also trigger malignant progression by modulating gene expression and inducing genetic instability. The relationship between microvasculature, perfusion and tumor hypoxia has been intensively studied and many computational simulations have been developed to model tissue O2 transport. Usually simplified 2D phantoms are used to investigate tumor hypoxia and it is assumed that vessels are perpendicular to the region of interest and randomly distributed across the domain. Such idealistic topology overlooks vascular heterogeneity and is not accurate enough to approximate real scenarios. In addition, experimental verification of the spatial gradient of computational simulations is not directly feasible. Realistic vasculature obtained from fluorescence imaging imported as geometry for partial differential equations solving did not receive necessary attention so far. Therefore, we established a computational simulation of in vivo conditions using experimental data obtained from dorsal skin window chamber tumor preparations in nude rats for the verification of computational results. Tumor microvasculature was assessed by fluorescence microscopy. Since the conventional finite difference method can hardly satisfy the real measurements, we established a finite element method (FEM) for the experimental data in this study. Realistic 2D tumor microvasculature was reconstructed by segmenting fluorescence images and then translated into FEM topology. O2 distributions and the O2 gradients were obtained by solving reaction-diffusion equations. The simulation results show that the development of tumor hypoxia is greatly influenced by the irregular architecture and function of microvascular networks.

Norspermidine changes the basic structure of S.mutans biofilm.

The factors regulating the assembly of the three-dimensional structure of Streptococcus mutans biofilms remain obscure. Polyamines are essential in biofilm formation of certain bacteria. Norspermidine, an unusual polyamine, has been a controversial polyamine that can lead to biofilm disassembly. However, the role of norspermidine in S. mutans biofilms remains unknown. Therefore, the present study investigated the impact of norspermidine on S. mutans biofilms. The different architectures of the biofilms in norspermidine and control groups indicated that the basic units, bacteria-exopolysaccharide units (BEUs), represent the exopolysaccharide (EPS) and bacterial assembly pattern in S. mutans biofilms. In addition, norspermidine inhibited S. mutans biofilm formation and changed the basic composition of the biofilm, which led to an unusual EPS architecture. Therefore, 5 mM norspermidine inhibited biofilm formation both by decreasing the rate of cell viability and changing the biofilm structure. Gene-expression microarray analysis indicated that the formation of an irregular architecture in the norspermidine group was potentially attributable to the downregulation of elements of the quorum-sensing system (by 2.7–15-fold). The present study suggested that the BEUs are a basic structure of S. mutans biofilm and its assembly is regulated majorly by the quorum-sensing system. Norspermidine can lead to structure change in BEUs by influencing S. mutans quorum-sensing system.

Altered Apical Morphology (Reverse Architecture): Use of Indirect Ultrasonic Technique for Orthograde MTA Placement in Maxillary Premolars.

Aim. To report the management and orthograde technique of MTA placement in case of reverse architecture maxillary premolars. Summary. Two cases of 17-year-old and 21-year-old female patients were referred to endodontic speciality for management of maxillary premolar having reverse architecture with wide immature open apex like a bell mouth. In both the cases, after control of intraradicular infection, it was decided to use MTA for apexification and obturation of canals. Orthograde placement of MTA is a challenging procedure in terms of length control and condensation especially in divergent irregular reverse architecture wide open apex. A novel technique with the help of finger plugger, sterilized paper point, and ultrasonic agitation for 3D compaction of MTA at apical reverse architecture was used. Thickening of the canal wall and complete apical closure were confirmed one year after the treatment.

Quantitative Analysis of the Enhanced Permeation and Retention (EPR) Effect.

Tumor vasculature is characterized by a variety of abnormalities including irregular architecture, poor lymphatic drainage, and the upregulation of factors that increase the paracellular permeability. The increased permeability is important in mediating the uptake of an intravenously administered drug in a solid tumor and is known as the enhanced permeation and retention (EPR) effect. Studies in animal models have demonstrated a cut-off size of 500 nm - 1 µm for molecules or nanoparticles to extravasate into a tumor, however, surprisingly little is known about the kinetics of the EPR effect. Here we present a pharmacokinetic model to quantitatively assess the influence of the EPR effect on the uptake of a drug into a solid tumor. We use pharmacokinetic data for Doxil and doxorubicin from human clinical trials to illustrate how the EPR effect influences tumor uptake. This model provides a quantitative framework to guide preclinical trials of new chemotherapies and ultimately to develop design rules that can increase targeting efficiency and decrease unwanted side effects in normal tissue.

Prevalence of Raynaud phenomenon and nailfold capillaroscopic abnormalities in Fabry disease: a cross-sectional study.

Fabry disease (FD) is a lysosomal disorder leading to progressive systemic involvement, including microvascular damage that leads to neurological and cardiovascular disorders. We hypothesize that the latter could be documented at an early stage by performing a microcirculation study with nailfold capillaroscopy and evaluation of Raynaud phenomenon.The objective was to measure the prevalence of Raynaud phenomenon and nailfold capillaroscopic abnormalities in FD.This cross-sectional study included a standardized questionnaire and a nailfold capillaroscopy that assessed previously reported patterns in FD (dystrophic and giant capillaries, avascular fields, irregular architecture, dilatation and density of capillaries, hemorrhage), and was conducted on 32 Fabry patients and 39 controls. Capillaroscopic photographs were reviewed by 2 independent blinded investigators.Twelve Fabry patients (38%) suffered from Raynaud phenomenon, 5 were males (ie, 50% of male Fabry patients), compared with 2 controls (13%) (P < 0.001), of whom none were males (P < 0.001). Raynaud phenomenon was concomitant or before the occurrence of pain in the extremities in 42% of Fabry patients.More ramified capillaries were significantly observed in Fabry patients (12/32, 38%) than in controls (5/39, 13%, P = 0.016).Secondary Raynaud phenomenon should lead to screening for FD, especially in men. By extension, in high-risk populations for FD, the presence of Raynaud phenomenon and ramified capillaries should be assessed.

Beamforming properties and design of the phased arrays in terms of irregular subarrays

Large phased arrays are often organised by subarrays given the current state of technology. The irregular subarray architecture, which can effectively mitigate the quantisation lobes, has received a renewed interest in recent years. Recent researches present some innovative particular irregular subarrays to provide practical means to eliminate the quantisation lobes using several (even only one) kinds of subarray. However, there is no single, neat theory of the irregularly partitioned array antennas in the literature. This study presents some derivations of the beamforming properties for arrays with arbitrary subarray partition to fill this gap. Derivations have led us to introduce a novel approach to assess the radiation properties which is useful for the systematic design of phased arrays. Numerical experiments are carried out to validate the authors’ derivations. Additionally, an elaborate example illustrates a design discipline for a limited-field-of-view array with polyomino-shaped subarrays.

A general data-driven algorithm for façade structure modeling using ground based laser data

Abstract. Façade reconstruction from laser point cloud has been an interesting subject in Photogrammetric community for the last two decades. However, due to the variety of architecture types and the nature of laser data, proposing a fully automatic modelling algorithm is still a challenge. Irregular architecture, density variation, occlusion and noise level are the main hindering factors of proposing a general model for façade reconstruction. This paper describes the sequences of an automatic data- driven method which starts from raw laser data and ends with object extraction. Statistical analysis was frequently utilized in segmentation, splitting line detection and object characterization. A rule-based modification method was employed to model the complexity of façade layout. Developed interface enables non-expert user to interact with modelling process by setting few parameters. The method was tested over a couple of datasets.

Electron paramagnetic resonance (EPR) investigation of skin structure of Psoriasis vulgaris

E paramagnetic resonance (EPR) spin-probe method was used to investigate structural aspects of psoriasis vulgaris stratum corneum (pv-SC). EPR spectra of the SC samples were analyzed using order parameter (S0) and rotational diffusion rates. A little, broad three-line pattern of 5-doxylstearic acid (5-DSA) in pv-SC was observed. The spectral pattern of pv-SC is quite different from those of control SC reported.The S0-values obtained for the pv-SC and the control were approximately 0.20 and 0.49, respectively. The statistical analysis suggests that the 0.20 value of pv-SC is significantly smaller than the 0.49 value of the control (p<0.01). The rotational diffusion rates for the probe motion in the SC were faster than those of the control. Moreover, there was no significant spectral difference of the glass-plate with the SC against the static magnetic field, except for the signal intensity.The present results suggest that the pv-SC is less rigid of the structure than that of the control SC, indicating irregular architecture of pv-SC.

Stratum Corneum Structure of Psoriasis Vulgaris Investigated by EPR Spin-Probe Method

Electron paramagnetic resonance (EPR) spin-probe method was used to investigate structural aspects of psoriasis vulgaris SC (pv-SC). EPR spectra of the SC samples were analyzed using order parameter (S 0) and rotational diffusion rates. A little, broad three-line pattern of 5-doxylstearic acid (spin probe) in pv-SC was observed. The spectral pattern of pv-SC is quite different from those of control SC reported. The S 0 values obtained for the pv-SC and the control were approximately 0.20 and 0.49, respectively. The statistical analysis suggests that the 0.20 value of pv-SC is significantly smaller than the 0.49 value of the control (p < 0.01). The rotational diffusion rates for the probe motion in the SC were faster than those of the control. Moreover, there was no spectral difference of the glass plate with the SC against the static magnetic field, except for the signal intensity. Therefore, the pv-SC is less rigid of the structure than that of the control SC, indicating irregular architecture of pv-SC. The present results suggest that the EPR assay is of great use for evaluating various SC function and can be extended to other skin diseases with abnormal keratinization.