Performance Improvement of Partial Least Squares Regression Soluble Solid Content Prediction Model Based on Adjusting Distance between Light Source and Spectral Sensor according to Apple Size.

Apples are widely cultivated in the Republic of Korea and are preferred by consumers for their sweetness. Soluble solid content (SSC) is measured non-destructively using near-infrared (NIR) spectroscopy; however, the SSC measurement error increases with the change in apple size since the distance between the light source and the near-infrared sensor is fixed. In this study, spectral characteristics caused by the differences in apple size were investigated. An optimal SSC prediction model applying partial least squares regression (PLSR) to three measurement conditions based on apple size was developed. The three optimal measurement conditions under which the Vis/NIR spectrum is less affected by six apple size levels (Levels I-VI) were selected. The distance from the apple center to the light source and that to the sensor were 125 and 75 mm (Distance 1), 123 and 75 mm (Distance 2), and 135 and 80 mm (Distance 3). The PLSR model applying multiplicative scatter correction pretreatment under Distance 3 measurement conditions showed the best performance for Level IV-sized apples (Rpre2 = 0.91, RMSEP = 0.508 °Brix). This study shows the possibility of improving the SSC prediction performance of apples by adjusting the distance between the light source and the NIR sensor according to fruit size.

Prediction of Soluble-Solid Content in Citrus Fruit Using Visible-Near-Infrared Hyperspectral Imaging Based on Effective-Wavelength Selection Algorithm.

Citrus fruits were sorted based on external qualities, such as size, weight, and color, and internal qualities, such as soluble solid content (SSC), acidity, and firmness. Visible and near-infrared (VNIR) hyperspectral imaging techniques were used as rapid and nondestructive techniques for determining the internal quality of fruits. The applicability of the VNIR hyperspectral imaging technique for predicting the SSC in citrus fruits was evaluated in this study. A VNIR hyperspectral imaging system with a wavelength range of 400-1000 nm and 100 W light source was used to acquire hyperspectral images from citrus fruits in two orientations (i.e., stem and calyx ends). The SSC prediction model was developed using partial least-squares regression (PLSR). Spectrum preprocessing, effective wavelength selection through competitive adaptive reweighted sampling (CARS), and outlier detection were used to improve the model performance. The performance of each model was evaluated using the coefficient of determination (R2) and root mean square error (RMSE). In the present study, the PLSR model was developed using only a citrus cultivar. The SSC prediction CARS-PLSR model with outliers removed exhibited R2 and RMSE values of approximatively 0.75 and 0.56 °Brix, respectively. The results of this study are expected to be useful in similar fields such as agricultural and food post-harvest management, as well as in the development of an online system for determining the SSC of citrus fruits.

The atlas of RNase H antisense oligonucleotide distribution and activity in the CNS of rodents and non-human primates following central administration.

Antisense oligonucleotides (ASOs) have emerged as a new class of drugs to treat a wide range of diseases, including neurological indications. Spinraza, an ASO that modulates splicing of SMN2 RNA, has shown profound disease modifying effects in Spinal Muscular Atrophy (SMA) patients, energizing efforts to develop ASOs for other neurological diseases. While SMA specifically affects spinal motor neurons, other neurological diseases affect different central nervous system (CNS) regions, neuronal and non-neuronal cells. Therefore, it is important to characterize ASO distribution and activity in all major CNS structures and cell types to have a better understanding of which neurological diseases are amenable to ASO therapy. Here we present for the first time the atlas of ASO distribution and activity in the CNS of mice, rats, and non-human primates (NHP), species commonly used in preclinical therapeutic development. Following central administration of an ASO to rodents, we observe widespread distribution and target RNA reduction throughout the CNS in neurons, oligodendrocytes, astrocytes and microglia. This is also the case in NHP, despite a larger CNS volume and more complex neuroarchitecture. Our results demonstrate that ASO drugs are well suited for treating a wide range of neurological diseases for which no effective treatments are available.

Performance Comparison of Tungsten-Halogen Light and Phosphor-Converted NIR LED in Soluble Solid Content Estimation of Apple.

A Tungsten-Halogen (TH) lamp is the most popular light source in NIR spectroscopy and hyperspectral imaging, which requires a warm-up to reach very high temperatures of up to 250 °C and take a long time for radiation stabilization. Consequently, it has a large enough volume to enable heat dissipation to prevent the thermal runaway of the electric circuit and turn out its power efficiency very low. These are major barriers for miniaturizing spectral systems and hyperspectral imaging devices. However, TH lamps can be replaced by pc-NIR LEDs in order to avoid high temperature and large volume. We compared the spectral emission of the available commercial pc-NIR LEDs under the same condition. As a replacement for the TH lamp, the VIS + NIR LED module was developed to combine a warm-white LED and pc-NIR LEDs. In order to feature out the availability of the VIS + NIR LED module against the TH lamp, they were used as the light source for evaluating the Soluble Solid Content (SSC) of an apple through VIS-NIR spectroscopy. The results show a remarkable feasibility in the performance of the partial least square (PLS) model using the VIS + NIR LED module; during PLS calibration, the correlation coefficient (R) values are 0.664 and 0.701, and the Mean Square Error (MSE) values are 0.681 and 0.602 for the TH lamp and VIS + NIR LED module, respectively. In VIS-NIR spectroscopy, this study indicates that the TH lamp could be replaceable with a warm-white LED and pc-NIR LEDs.

Towards a therapy for Angelman syndrome by targeting a long non-coding RNA.

Angelman syndrome is a single-gene disorder characterized by intellectual disability, developmental delay, behavioural uniqueness, speech impairment, seizures and ataxia. It is caused by maternal deficiency of the imprinted gene UBE3A, encoding an E3 ubiquitin ligase. All patients carry at least one copy of paternal UBE3A, which is intact but silenced by a nuclear-localized long non-coding RNA, UBE3A antisense transcript (UBE3A-ATS). Murine Ube3a-ATS reduction by either transcription termination or topoisomerase I inhibition has been shown to increase paternal Ube3a expression. Despite a clear understanding of the disease-causing event in Angelman syndrome and the potential to harness the intact paternal allele to correct the disease, no gene-specific treatment exists for patients. Here we developed a potential therapeutic intervention for Angelman syndrome by reducing Ube3a-ATS with antisense oligonucleotides (ASOs). ASO treatment achieved specific reduction of Ube3a-ATS and sustained unsilencing of paternal Ube3a in neurons in vitro and in vivo. Partial restoration of UBE3A protein in an Angelman syndrome mouse model ameliorated some cognitive deficits associated with the disease. Although additional studies of phenotypic correction are needed, we have developed a sequence-specific and clinically feasible method to activate expression of the paternal Ube3a allele.

Needle-free pneumatic injection device; histologic assessment using a rat model and parameter comparison in predicting collagen synthesis degree.

BACKGROUND: Needle-free pneumatic injections have been recently introduced to the field of dermatology to inject such substances as hyaluronic acid. However, data on the influence of various pneumatic injection parameters on collagen synthesis are lacking. OBJECTIVE: Compare the effect of diameter, pressure, and volume of a pneumatic injection jet on collagen synthesis and fluid dispersion pattern using a rat model. Investigate if the total work force of the injection jet is useful in predicting the degree of collagen synthesis. MATERIALS AND METHODS: We injected fluid with 1 mg/ml of hyaluronic concentration to adult rats. Different injection pressures and volumes were tested using devices with nozzles of different diameters. Collagen synthesis areas were then measured, and statistical analyses were performed. RESULTS: The area of collagen fibers increased for up to two months. The injection pressure and volume did not correlate with the degree of collagen synthesis. The nozzle diameter showed a significant after two and four weeks of injection. The total work force correlated with collagen synthesis 2, 4, and 8 weeks post-injection. (P = 0.043, 0.027, and 0.000, respectively). CONCLUSION: Collagen formation is more prominent 2 months post-hyaluronic acid injection than after 1 month when using a needle-free pneumatic injection device. The total work force, which is affected by both the nozzle diameter and injection pressure, can be helpful in predicting the degree of collagen synthesis. Lasers Surg. Med. 51:278-285, 2019. © 2019 Wiley Periodicals, Inc.

Prospective Evaluation of Atrophic Acne Scars on the Face With Needle-Free High-Pressure Pneumatic Injection: Quantitative Volumetric Scar Improvement.

BACKGROUND: Atrophic acne facial scars still pose a treatment challenge. Needle-free high-pressure pneumatic injection has recently been introduced; however, few studies exist regarding its effectiveness. OBJECTIVE: To evaluate the efficacy and safety of pneumatic injection for treating atrophic acne scars using a 3-dimensional optical profiling system. METHODS AND MATERIALS: A pneumatic injection device with a 0.2-mm nozzle diameter, 50% pressure power, and 85-µL injection volume was used. The degree of depression was examined and analyzed using a 3-dimensional optical profiling system and clinical photographs. The patients also evaluated any side effects. Each subject underwent a single treatment session and was followed up after 1 and 2 months. RESULTS: A total of 13 atrophic acne scars from 10 Korean men and women aged 20 to 29 (mean age 25.8 ± 2.4) years were studied. The mean scar volume values were 0.964, 0.741, and 0.566 mm, respectively, at baseline, 1 month, and 2 months after the injection. Scar volumes after 2 months were significantly different compared with baseline volumes. However, there was no significant difference between the baseline and 1-month volumes. CONCLUSION: Treatment with pneumatic injection is safe and effective in reducing atrophic acne facial scars; it results in quantitative improvement in scar volumes.

Effects on murine behavior and lifespan of selectively decreasing expression of mutant huntingtin allele by supt4h knockdown.

Production of protein containing lengthy stretches of polyglutamine encoded by multiple repeats of the trinucleotide CAG is a hallmark of Huntington's disease (HD) and of a variety of other inherited degenerative neurological and neuromuscular disorders. Earlier work has shown that interference with production of the transcription elongation protein SUPT4H results in decreased cellular capacity to transcribe mutant huntingtin gene (Htt) alleles containing long CAG expansions, but has little effect on expression of genes containing short CAG stretches. zQ175 and R6/2 are genetically engineered mouse strains whose genomes contain human HTT alleles that include greatly expanded CAG repeats and which are used as animal models for HD. Here we show that reduction of SUPT4H expression in brains of zQ175 mice by intracerebroventricular bolus injection of antisense 2'-O-methoxyethyl oligonucleotides (ASOs) directed against Supt4h, or in R6/2 mice by deletion of one copy of the Supt4h gene, results in a decrease in mRNA and protein encoded specifically by mutant Htt alleles. We further show that reduction of SUPT4H in mouse brains is associated with decreased HTT protein aggregation, and in R6/2 mice, also with prolonged lifespan and delay of the motor impairment that normally develops in these animals. Our findings support the view that targeting of SUPT4H function may be useful as a therapeutic countermeasure against HD.

Comparative study of dual-pulsed 1064 nm Q-switched Nd:YAG laser and single-pulsed 1064 nm Q-switched Nd:YAG laser by using zebrafish model and prospective split-face analysis of facial melasma.

BACKGROUND: Recently dual-pulsed low-fluence 1064-nm Q-switched Nd:YAG (QSNY) laser has been developed for reducing complication during melasma treatment. OBJECTIVE: Comparison of the efficacy and safety between dual-pulsed mode and single-pulsed mode for the treatment of melasma. MATERIALS AND METHODS: In preclinical study, adult zebrafish were irradiated with dual-pulsed and single-pulsed mode. Changes of melanophore and cell death were assessed. In split-face clinical study, dual-pulsed and single-pulsed mode were irradiated on the left and right side of the face, respectively. L* value, clinical digital photos, modified Melasma Area and Severity Index (MASI) scores, and side effects were measured. RESULTS: As compared to single-pulsed mode and dual-pulsed mode with longer intervals, zebrafish melanophore was cleared quickly at dual-pulsed mode with 80-µsec interval and 0.3 J/cm2 fluence. Dual-pulsed mode showed the least regeneration of melanophore at 4 weeks after irradiation and no cell death was observed with 80-µsec interval. Both pulse modes improved melasma significantly but modified MASI score and L* value were not significantly different between each other. Lesser pain and shorter duration of post-laser erythema were observed with dual-pulsed mode. CONCLUSION: Dual-pulsed mode was as effective as single-pulsed mode for the treatment of melasma and revealed less side effects.

A Mechanism for Reliable Mobility Management for Internet of Things Using CoAP.

Under unreliable constrained wireless networks for Internet of Things (IoT) environments, the loss of the signaling message may frequently occur. Mobile Internet Protocol version 6 (MIPv6) and its variants do not consider this situation. Consequently, as a constrained device moves around different wireless networks, its Internet Protocol (IP) connectivity may be frequently disrupted and power can be drained rapidly. This can result in the loss of important sensing data or a large delay for time-critical IoT services such as healthcare monitoring and disaster management. This paper presents a reliable mobility management mechanism in Internet of Things environments with lossy low-power constrained device and network characteristics. The idea is to use the Internet Engineering Task Force (IETF) Constrained Application Protocol (CoAP) retransmission mechanism to achieve both reliability and simplicity for reliable IoT mobility management. Detailed architecture, algorithms, and message extensions for reliable mobility management are presented. Finally, performance is evaluated using both mathematical analysis and simulation.

Nonsense-mediated decay as a terminating mechanism for antisense oligonucleotides.

Antisense oligonucleotides (ASOs) are synthetic oligonucleotides that alter expression of disease-associated transcripts via Watson-Crick hybridization. ASOs that function through RNase H or the RNA-induced silencing complex (RISC) result in enzymatic degradation of target RNA. ASOs designed to sterically block access of proteins to the RNA modulate mRNA metabolism but do not typically cause degradation. Here, we rationally design steric blocking ASOs to promote mRNA reduction and characterize the terminating mechanism. Transfection of ASOs complementary to constitutive exons in STAT3 and Sod1 results in greater than 70% reduction of mRNA and protein. The ASOs promote aberrant exon skipping and generation of premature termination codon (PTC)-containing mRNAs. We inhibit the nonsense-mediated mRNA decay (NMD) pathway and show that the PTC-containing mRNAs are recognized by the UPF1 ATPase, cleaved by the SMG6 endonuclease and degraded by the XRN1 cytoplasmic exonuclease. NMD surveillance, however, does not entirely explain the mechanism of decreased STAT3 expression. In addition to exon skipping, ASO treatment causes intron retention and reduction of chromatin-associated STAT3 mRNA. The application of steric blocking ASOs to promote RNA degradation allows one to explore more nucleotide modifications than tolerated by RNase H or RISC-dependent ASOs, with the goal of improving ASO drug properties.

Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration.

Expanded hexanucleotide repeats in the chromosome 9 open reading frame 72 (C9orf72) gene are the most common genetic cause of ALS and frontotemporal degeneration (FTD). Here, we identify nuclear RNA foci containing the hexanucleotide expansion (GGGGCC) in patient cells, including white blood cells, fibroblasts, glia, and multiple neuronal cell types (spinal motor, cortical, hippocampal, and cerebellar neurons). RNA foci are not present in sporadic ALS, familial ALS/FTD caused by other mutations (SOD1, TDP-43, or tau), Parkinson disease, or nonneurological controls. Antisense oligonucleotides (ASOs) are identified that reduce GGGGCC-containing nuclear foci without altering overall C9orf72 RNA levels. By contrast, siRNAs fail to reduce nuclear RNA foci despite marked reduction in overall C9orf72 RNAs. Sustained ASO-mediated lowering of C9orf72 RNAs throughout the CNS of mice is demonstrated to be well tolerated, producing no behavioral or pathological features characteristic of ALS/FTD and only limited RNA expression alterations. Genome-wide RNA profiling identifies an RNA signature in fibroblasts from patients with C9orf72 expansion. ASOs targeting sense strand repeat-containing RNAs do not correct this signature, a failure that may be explained, at least in part, by discovery of abundant RNA foci with C9orf72 repeats transcribed in the antisense (GGCCCC) direction, which are not affected by sense strand-targeting ASOs. Taken together, these findings support a therapeutic approach by ASO administration to reduce hexanucleotide repeat-containing RNAs and raise the potential importance of targeting expanded RNAs transcribed in both directions.

Rescue of gene-expression changes in an induced mouse model of spinal muscular atrophy by an antisense oligonucleotide that promotes inclusion of SMN2 exon 7.

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by disruption of the survival motor neuron 1 (SMN1) gene, partly compensated for by the paralogous gene SMN2. Exon 7 inclusion is critical for full-length SMN protein production and occurs at a much lower frequency for SMN2 than for SMN1. Antisense oligonucleotide (ASO)-mediated blockade of an intron 7 splicing silencer was previously shown to promote inclusion of SMN2 exon 7 in SMA mouse models and mediate phenotypic rescue. However, downstream molecular consequences of this ASO therapy have not been defined. Here we characterize the gene-expression changes that occur in an induced model of SMA and show substantial rescue of those changes in central nervous system tissue upon intracerebroventricular administration of an ASO that promotes inclusion of exon 7, with earlier administration promoting greater rescue. This study offers a robust reference set of preclinical pharmacodynamic gene expression effects for comparison of other investigational therapies for SMA.

CoAP-Based Mobility Management for the Internet of Things.

Most of the current mobility management protocols such as Mobile IP and its variants standardized by the IETF may not be suitable to support mobility management for Web-based applications in an Internet of Things (IoT) environment. This is because the sensor nodes have limited power capacity, usually operating in sleep/wakeup mode in a constrained wireless network. In addition, sometimes the sensor nodes may act as the server using the CoAP protocol in an IoT environment. This makes it difficult for Web clients to properly retrieve the sensing data from the mobile sensor nodes in an IoT environment. In this article, we propose a mobility management protocol, named CoMP, which can effectively retrieve the sensing data of sensor nodes while they are moving. The salient feature of CoMP is that it makes use of the IETF CoAP protocol for mobility management, instead of using Mobile IP. Thus CoMP can eliminates the additional signaling overhead of Mobile IP, provides reliable mobility management, and prevents the packet loss. CoMP employs a separate location management server to keep track of the location of the mobile sensor nodes. In order to prevent the loss of important sensing data during movement, a holding mode of operation has been introduced. All the signaling procedures including discovery, registration, binding and holding have been designed by extending the IETF CoAP protocol. The numerical analysis and simulation have been done for performance evaluation in terms of the handover latency and packet loss. The results show that the proposed CoMP is superior to previous mobility management protocols, i.e., Mobile IPv4/v6 (MIPv4/v6), Hierarchical Mobile IPv4/v6 (HMIPv4/v6), in terms of the handover latency and packet loss.

Pharmacology of a central nervous system delivered 2'-O-methoxyethyl-modified survival of motor neuron splicing oligonucleotide in mice and nonhuman primates.

Spinal muscular atrophy (SMA) is a debilitating neuromuscular disease caused by the loss of survival of motor neuron (SMN) protein. Previously, we demonstrated that ISIS 396443, an antisense oligonucleotide (ASO) targeted to the SMN2 pre-mRNA, is a potent inducer of SMN2 exon 7 inclusion and SMN protein expression, and improves function and survival of mild and severe SMA mouse models. Here, we demonstrate that ISIS 396443 is the most potent ASO in central nervous system (CNS) tissues of adult mice, compared with several other chemically modified ASOs. We evaluated methods of ISIS 396443 delivery to the CNS and characterized its pharmacokinetics and pharmacodynamics in rodents and nonhuman primates (NHPs). Intracerebroventricular bolus injection is a more efficient method of delivering ISIS 396443 to the CNS of rodents, compared with i.c.v. infusion. For both methods of delivery, the duration of ISIS 396443-mediated SMN2 splicing correction is long lasting, with maximal effects still observed 6 months after treatment discontinuation. Administration of ISIS 396443 to the CNS of NHPs by a single intrathecal bolus injection results in widespread distribution throughout the spinal cord. Based upon these preclinical studies, we have advanced ISIS 396443 into clinical development.

Synthetic oligonucleotides recruit ILF2/3 to RNA transcripts to modulate splicing.

We describe a new technology for recruiting specific proteins to RNA through selective recognition of heteroduplexes formed with chemically modified antisense oligonucleotides (ASOs). Typically, ASOs function by hybridizing to their RNA targets and blocking the binding of single-stranded RNA-binding proteins. Unexpectedly, we found that ASOs with 2'-deoxy-2'-fluoro (2'-F) nucleotides, but not with other 2' chemical modifications, have an additional property: they form heteroduplexes with RNA that are specifically recognized by the interleukin enhancer-binding factor 2 and 3 complex (ILF2/3). 2'-F ASO-directed recruitment of ILF2/3 to RNA can be harnessed to control gene expression by modulating alternative splicing of target transcripts. ILF2/3 recruitment to precursor mRNA near an exon results in omission of the exon from the mature mRNA, both in cell culture and in mice. We discuss the possibility of using chemically engineered ASOs that recruit specific proteins to modulate gene expression for therapeutic intervention.

Value of CT for ERCP Endoscopists to Identify the Type of Gastroenteric Anastomosis in Patients with Previous Subtotal Gastrectomy.

UNLABELLED: Background/Aims: The aim of this study was to evaluate whether endoscopic retrograde cholangiopancreatography (ERCP) endoscopists can distinguish the type of gastroenteric anastomosis in patients with previous subtotal gastrectomy based on CT findings, particularly in biliary emergencies. METHODOLOGY: A total of 70 abdominal CT scans from patients who had undergone gastrectomy (n = 36, Billroth I; n = 34, Billroth II) were enrolled. The shuffled images were reviewed by 3 ERCP endoscopists blinded to clinical data. The endoscopists were asked to provide the most probable type of anastomosis. The sensitivity, specificity and interobserver agreement were analyzed for identifying Billroth II gastrectomy. RESULTS: The ERCP endoscopists were able to identify the type of anastomosis based on CT findings with a sensitivity, specificity and interobserver agreement of 100%, 97.2%, and 0.98, respectively. The key CT features for distinguishing Billroth II gastrectomy from Billroth I gastrectomy were: i) loss of continuity between the remnant stomach and duodenum; ii) less distended duodenal bulb; iii) the presence of a closed duodenal stump with surgical staples and iv) the presence of continuity between the remnant stomach and the jejunum. CONCLUSIONS: ERCP endoscopists were able to use CT findings to distinguish the type of gastroenteric anastomosis in patients with previous gastrectomy.

The Loop-Tip Wire for Selective Cannulation during ERCP in Patients with Billroth II Anastomosis: A Preliminary Feasibility Study.

BACKGROUND/AIMS: Selective cannulation of common bile duct remains technically challenging in patients with Billroth II anastomosis due to an altered anatomy. We aimed to determine the feasibility of performing wire-assisted cannulation using a loop-tip wire during ERCP in patients with Billroth II anastomosis. METHODOLOGY: We retrospectively analyzed a database of nine patients with Billroth II anastomosis who underwent ERCP using a loop-tip wire from January 2009 to July 2013 in the Hallym University Sacred Heart Hospital. Clinical characteristics and procedure-associated clinical outcomes were analyzed. RESULTS: The mean age of the patients was 73.7 years, and the male/female ratio was 2:1. The success rate of selective biliary cannulation was 77.8%. The mean cannulation time was 3.6 minutes (range, 1-9 minutes). Two patients who had failed in selective cannulation underwent infundibulotomy using a needle-knife papillotome, but one of the two patients had failed in biliary stone removal and finally underwent surgery. Six patients underwent endoscopic sphincterotomy. Complete clearance of bile duct stones was achieved in seven patients in one session. There was one case of mild post-ERCP pancreatitis (11.1%). CONCLUSIONS: The loop-tip wire can be an alternative instrument for wire-assisted selective cannulation in patients with Billroth II anastomosis.

Emergence of two distinct phase transitions in monolayer CoSe2 on graphene.

Dimensional modifications play a crucial role in various applications, especially in the context of device miniaturization, giving rise to novel quantum phenomena. The many-body dynamics induced by dimensional modifications, including electron-electron, electron-phonon, electron-magnon and electron-plasmon coupling, are known to significantly affect the atomic and electronic properties of the materials. By reducing the dimensionality of orthorhombic CoSe2 and forming heterostructure with bilayer graphene using molecular beam epitaxy, we unveil the emergence of two types of phase transitions through angle-resolved photoemission spectroscopy and scanning tunneling microscopy measurements. We disclose that the 2 × 1 superstructure is associated with charge density wave induced by Fermi surface nesting, characterized by a transition temperature of 340 K. Additionally, another phase transition at temperature of 160 K based on temperature dependent gap evolution are observed with renormalized electronic structure induced by electron-boson coupling. These discoveries of the electronic and atomic modifications, influenced by electron-electron and electron-boson interactions, underscore that many-body physics play significant roles in understanding low-dimensional properties of non-van der Waals Co-chalcogenides and related heterostructures.

Amelanotic acral melanomas: clinicopathological, BRAF mutation, and KIT aberration analyses.

BACKGROUND: Amelanotic acral melanoma (AAM) is very rare and difficult to diagnose both clinically and pathologically. Complete-type AAM shows no black to brown pigmentation in the lesion, whereas incomplete-type AAM shows focal or subtle pigmentation. AAM has been the subject of few investigations. OBJECTIVES: We analyzed the clinicopathological features, BRAF mutations, and KIT aberrations in 35 Korean AAM cases. METHODS: We included 28 cases of complete-type and 7 cases of incomplete-type AAM. RESULTS: In all, 26 AAMs (45.7%) were located on the feet of patients, 21 of which (82.9%) showed ulceration. Sixteen cases developed in subungual areas. Nodular melanoma was the most common histopathological subtype (63.6%). The most frequent cell types affected were epithelioid and spindled. HMB-45 staining was strongly positive in 66.7% of AAMs; 4 (12.1%) were negative for HMB-45, and 3 of these were complete-type AAMs. Of 33 total patients, BRAF mutations were detected in 2 AAM cases, and KIT aberrations were present in 11 cases (33.3%). Four cases (12.1%), all of which were complete-type AAMs, had KIT mutations. KIT aberrations were weakly correlated with c-kit staining. Twenty patients were TNM stage I or II, and mean survival was 30.14 ± 4.54 months. LIMITATIONS: The study is limited by the small number of patients. CONCLUSION: Physicians should be aware of rare and hard-to-diagnose AAMs. We expect that tyrosine kinase inhibitors would be effective for KIT-mutated patients with complete-type AAMs.