Diagnostic Assessment of Deep Learning Algorithms for Frozen Tissue Section Analysis in Women with Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Assessing the metastasis status of the sentinel lymph nodes (SLNs) for hematoxylin and eosin–stained frozen tissue sections by pathologists is an essential but tedious and time-consuming task that contributes to accurate breast cancer staging. This study aimed to review a challenge competition (HeLP 2019) for the development of automated solutions for classifying the metastasis status of breast cancer patients. @*Materials and Methods@#A total of 524 digital slides were obtained from frozen SLN sections: 297 (56.7%) from Asan Medical Center (AMC) and 227 (43.4%) from Seoul National University Bundang Hospital (SNUBH), South Korea. The slides were divided into training, development, and validation sets, where the development set comprised slides from both institutions and training and validation set included slides from only AMC and SNUBH, respectively. The algorithms were assessed for area under the receiver operating characteristic curve (AUC) and measurement of the longest metastatic tumor diameter. The final total scores were calculated as the mean of the two metrics, and the three teams with AUC values greater than 0.500 were selected for review and analysis in this study. @*Results@#The top three teams showed AUC values of 0.891, 0.809, and 0.736 and major axis prediction scores of 0.525, 0.459, and 0.387 for the validation set. The major factor that lowered the diagnostic accuracy was micro-metastasis. @*Conclusion@#In this challenge competition, accurate deep learning algorithms were developed that can be helpful for making a diagnosis on intraoperative SLN biopsy. The clinical utility of this approach was evaluated by including an external validation set from SNUBH.

Reverse engineering technique on the evaluation of impression accuracy in angulated implants / 대한치과보철학회지

Purpose@#The aim of this study was (1) to compare the reverse engineering technique with other existing measurement methods and (2) to analyze the effect of implant angulations and impression coping types on implant impression accuracy with reverse engineering technique. @*Materials and methods@#Three different master models were fabricated and the distance between the two implant center points in parallel master model was measured with different three methods; digital caliper measurement (Group DC), optical measuring (Group OM), and reverse engineering technique (Group RE). The 90 experimental models were fabricated with three types of impression copings for the three different implant angulation and the angular and distance error rate were calculated. One-way ANOVA was used for comparison among the evaluation methods (P .05). The standard deviations in reverse engineering were much lower than those of digital caliper and optical measurement. Hybrid groups had no significant difference from the pick-up groups in distance error rates (P > .05). @*Conclusion@#The reverse engineering technique demonstrated its potential as an evaluation technique of 3D accuracy of impression techniques.

Reverse engineering technique on the evaluation of impression accuracy in angulated implants / 대한치과보철학회지

Purpose@#The aim of this study was (1) to compare the reverse engineering technique with other existing measurement methods and (2) to analyze the effect of implant angulations and impression coping types on implant impression accuracy with reverse engineering technique. @*Materials and methods@#Three different master models were fabricated and the distance between the two implant center points in parallel master model was measured with different three methods; digital caliper measurement (Group DC), optical measuring (Group OM), and reverse engineering technique (Group RE). The 90 experimental models were fabricated with three types of impression copings for the three different implant angulation and the angular and distance error rate were calculated. One-way ANOVA was used for comparison among the evaluation methods (P .05). The standard deviations in reverse engineering were much lower than those of digital caliper and optical measurement. Hybrid groups had no significant difference from the pick-up groups in distance error rates (P > .05). @*Conclusion@#The reverse engineering technique demonstrated its potential as an evaluation technique of 3D accuracy of impression techniques.

Effects of relining materials on the flexural strength of relined thermoplastic denture base resins

PURPOSE: The aim of this study was to evaluate the effects of relining materials on the flexural strength of relined thermoplastic denture base resins (TDBRs). MATERIALS AND METHODS: For shear bond strength testing, 120 specimens were fabricated using four TDBRs (EstheShot-Bright, Acrytone, Valplast, Weldenz) that were bonded with three autopolymerizing denture relining resins (ADRRs: Vertex Self-Curing, Tokuyama Rebase, Ufi Gel Hard) with a bond area of 6.0 mm in diameter and were assigned to each group (n=10). For flexural strength testing, 120 specimens measuring 64.0×10.0×3.3 mm (ISO-1567:1999) were fabricated using four TDBRs and three ADRRs and were assigned to each group (n=10). The thickness of the specimens measured 2.0 mm of TDBR and 1.3 mm of ADRR. Forty specimens using four TDBRs and 30 specimens using ADRRs served as the control. All specimens were tested on a universal testing machine. For statistical analysis, Analysis of variance (ANOVA) with Tukey's test as post hoc and Spearman's correlation coefficient analysis (P=.05) were performed. RESULTS: Acry-Tone showed the highest shear bond strength, while Weldenz demonstrated the lowest bond strength between TDBR and ADRRs compared to other groups. EstheShot-Bright exhibited the highest flexural strength, while Weldenz showed the lowest flexural strength. Relined EstheShot-Bright demonstrated the highest flexural strength and relined Weldenz exhibited the lowest flexural strength (P < .05). Flexural strength of TDBRs (P=.001) and shear bond strength (P=.013) exhibited a positive correlation with the flexural strength of relined TDBRs. CONCLUSION: The flexural strength of relined TDBRs was affected by the flexural strength of the original denture base resins and bond strength between denture base resins and relining materials.

Shear bond strength of composite resin to high performance polymer PEKK according to surface treatments and bonding materials

PURPOSE: The object of the present study was to evaluate the shear bonding strength of composite to PEKK by applying several methods of surface treatment associated with various bonding materials. MATERIALS AND METHODS: One hundred and fifty PEKK specimens were assigned randomly to fifteen groups (n = 10) with the combination of three different surface treatments (95% sulfuric acid etching, airborne abrasion with 50 µm alumina, and airborne abrasion with 110 µm silica-coating alumina) and five different bonding materials (Luxatemp Glaze & Bond, Visio.link, All-Bond Universal, Single Bond Universal, and Monobond Plus with Heliobond). After surface treatment, surface roughness and contact angles were examined. Topography modifications after surface treatment were assessed with scanning electron microscopy. Resin composite was mounted on each specimen and then subjected to shear bond strength (SBS) test. SBS data were analyzed statistically using two-way ANOVA, and post-hoc Tukey's test (P<.05). RESULTS: Regardless of bonding materials, mechanical surface treatment groups yielded significantly higher shear bonding strength values than chemical surface treatment groups. Unlike other adhesives, MDP and silane containing self-etching universal adhesive (Single Bond Universal) showed an effective shear bonding strength regardless of surface treatment method. CONCLUSION: Mechanical surface treatment behaves better in terms of PEKK bonding. In addition, self-etching universal adhesive (Single Bond Universal) can be an alternative bonding material to PEKK irrespective of surface treatment method.

Effect of Egg White Elimination Diet on Clinical Progress and Specific IgE Levels in Egg White Sensitized Children with Atopic Dermatitis / 소아알레르기및호흡기학회지

PURPOSE: Food allergies play a major role in childhood atopic dermatitis. Egg white is the most common causative allergen in IgE mediated food allergies, and the only treatment is complete elimination of egg white from diet. The purpose of this study is to evaluate the effect of an egg white elimination diet on clinical progress and egg white-specific IgE concentration in childhood atopic dermatitis. METHOD: In 20 children with mild to severe atopic dermatitis, clinical progress was monitored by Jakob's atopic dermatitis grading system, and serum specific-IgE levels to six common food allergens and two house dust mites were measured by CAP-FEIA. RESULTS: In the study subjects, eight patients had been exposed to egg before diagnosis. During the six to 48 months of egg white elimination diet, clinical symptoms and signs were improved in 15 out of 20 patients. However, egg white-specific IgE levels were reduced by less than 1.20 kU/L (the cut off level suggesting immunological tolerance) in only seven patients. In the five patients with clinically persistent atopic dermatitis, egg white-specific IgE levels were 10.6-100 kU/L and house dust mite-specific IgE levels were 25.9-100 kU/L at the time of final examination. CONCLUSION: After 6-48 months of the egg white elimination diet, 75% of egg allergic infants and children with atopic dermatitis showed clinical improvement of atopic dermatitis. However, it is suggested that the patients need more than 1-3 years of a complete elimination diet to obtain immunological tolerance determined by egg white-specific IgE levels.

Allergen and chow-protein stimulated splenocyte cytokine productions in buckwheat allergic mice / 천식및알레르기

BACKGROUND AND OBJECTIVE: Normal gut immune response to ingestive food proteins is induction of immune tolerance rather than sensitization, even in atopic individuals. Very restricted kinds of food antigens have been known to cause allergic sensitization in humans. To evaluate the differences of systemic T-cell immune responses to sensitized antigen and regular chow-protein, we performed this study. SUBJECTS AND METHODS: Eight naive female, 5-week-old C3H/HeJ mice were grown under the regular mouse chow feeding condition for 4 weeks. During that period, Group I mice were sensitized with buckwheat extract(1mg/dose) mixed with cholera toxin(10 microgram/dose) by intragastric administration at day1, 2, 3, 7, and 21. The sera were obtained at weekly intervals to measure buckwheat-specific and chow-protein-specific IgE, IgG1 and IgG2a antibodies. Splenocyte proliferation assays and cytokine productions were evaluated with buckwheat. chow-protein. and Con A stimulation. Levels of antibodies (IgE, IgG1, IgG2a) and cytokines (IL-4, IL-10, IL-12, INF-gamma were measured by ELISA. RESULTS: The levels of buckwheat specific IgE, IgG1 and IgG2a were markedly increased in Group I mice, but not in Group II mice. Chow-protein specific IgE and IgG1 antibodies were not increased in both groups of mice. The degrees of buckwheat-specific and chow-protein-specific splenocyte proliferations showed low-grade(SI: 6.68 and 4.48. respectively) compared to those by Con A stimulation(SI : 58). Buckwheat stimulated IL-4 productions were markedly increased in Group I mice, which were higher than Con A stimulated production. INF-gamma production was increased in Group I mice by buckwheat stimulation, and in both groups of mice by Con A stimulation. IL-12 production was shown in Con A stimulated culture supernatants in both groups of mice, but in Group I mice with buckwheat stimulation. IL-10 productions were increased in Group I mice with buckwheat, Con A, and chow-protein stimulations, furthermore, markedly increased IL-10 levels were also shown in chow-protein stimulated splenocyte cultures in both groups of mice. CONCLUSION: While Th1 and Th2 immune responses were induced by intragastricly sensitized buckwheat extract, only regulatory immune responses were dominated by regular chow proteins in this system. The minimum ability of chow-protein specific splenocyte proliferation was preserved and IL-10 was the unique cytokine produced by chow-protein simulation.

A Study on the Animal Epithelium as A Causative Allergen in Children with Asthma and Rhinitis / 소아알레르기및호흡기학회지

PURPOSE: The exposure to domestic animals has been increased, but there is no systematic evaluation for the clinical importance of animal antigens in Korea. The purpose of this study is to evaluate the significance of animal epithelial antigens as the causative allergens in childhood asthma and rhinitis. METHODS: In 228 children with asthma and rhinitis, allergic skin tests were done with 72 extracts, including 5 animal epithelial antigens. RESULTS: According to the results of allergy skin tests, 208 out of 228 children showed positive skin reactions to more than one antigens, and 128(61.4%) showed positive reactions to animal epithelial extracts. Among them, 17(8.1%) were mites non-sensitive to house dust and sensitive to animal epithelium. The positive reaction to each antigens were as follows:D. farinae(72.6%), D. pteronyssinus(69.7%), rabbit(40.3%), cat(33.1%), dog(24.0%), horse(16.8 %), and cow(14.9%). The degree of skin reactions to animal epithelial antigens were weaker than those to house dust mites. The positive concordance rates between skin tests and specific IgE reactions to D. pteronyssinus and cat/dog were 89.1%, and 25.9%, respectively. We experienced six patients with asthma and rhinitis who suspected animal epithelium as a causative allergen. CONCLUSION: Up to 61.4% of children with respiratory allergy showed positive reactions to animal epithelial extracts and 8.1% of them were house dust mites non-sensitive cases. Therefore, animal epithelium should be investigated as a causative allergen when skin reactions were strong and showed positive specific IgE antibodies.

Age-dependent changes of B cell and T cell-mediated immune responses in naive C3H/HeJ mice under regular mouse chow feeding conditions / 천식및알레르기

BACKGROUND AND OBJECTIVE: Murine system for studying allergic diseases has been popular in the fields of food allergy and development of their therapeutic strategies. However, there has been no information about the age-dependent changes of natural immune responses of naive C3H/HeJ mice. The purpose of this study was to evaluate the age-dependent changes of B and T-cell mediated immunologic parameters in naive C3H/HeJ mice, which can provide information for experimental planning and analysis of research results. SUBJECTS AND METHODS: Eight naive, female, 5-week-old C3H/HeJ mice were grown under the regular mouse chow feeding conditions for 6 weeks. Sera were obtained at week (w) 5, w6, w8 and w10 for measuring total and chow-specific IgE, IgG1 and IgG2a antibodies. Splenocyte proliferation (at w8 and w10) and cytokine production (at w6, w8 and w10) were evaluated with or without Con A stimulation with pooled splenocytes from two mice of each age group. Serum antibodies and cytokines (IL-4, IL-5, IL-12, INF-gamma, TGF-beta1) were measured by ELISA. Using RT-PCR, IL-4 and INF-gamma mRNA expressions were measured in Peyer's patch and spleen tissue at w10. RESULTS: The levels of total IgE and IgG1 were increased by age while the level of IgG2a was decreased. Chow-specific IgE and IgG2a responses were neglectable through out the whole experimental period (20-30 ng/ml or less). Chow-specific IgG1 levels were measured in the significant concentrations (200-300 ng/ml) but there was no age-dependent change through out the experiment. Con A stimulated-splenocyte proliferation indexes were variable according to the culture-durations and ages of mice. The higher proliferation indexes were observed in the wells receiving thymidine pulse at 48-hour culture, especially in the mice at w10. Con A stimulated IL-4 production in the 72-hour splenocyte culture supernatant was significantly increased at w8, and w10 while INF-gamma production increased only at w10. The changes in the production of IL-5, IL-12 and TGF-beta did not provide significant information in the present study. The ratio of IL-4/IFN-gamma mRNA expression was higher in Peyer's patch than in the spleen. CONCLUSION: The changes of B-cell and T-cell mediated immunologic parameters were complex and variable according to the age in naive C3H/HeJ mice under regular chow feeding conditions. For that reason, the information from the present study needs to be considered in the course of planning or analysing research/data using murine systems.

Comparison of child behavior checklist between allergic and non-allergic patients / 천식및알레르기

BACKGROUND AND OBJECTIVE: There have been several reports suggesting close relationships bet- ween problem behavior syndrome scale and/or social competence scale and pediatric allergic disorders such as bronchial asthma and atopic dermatitis. The aim of the present study was to confirm these relationships. We compared the behavioral symptoms and social competence scale between allergic and non-allergic patient groups using Korean-Child Behavior Checklist (K- CBCL). MATERIALS AND METHOD: One hundred and seventy-one subjects(aged 4-11 years) were enro- lled in this study. Allergy patient group(N=84) was divided into 4 subgroups, according to the allergic diseases such as atopic asthma(Group 1, BA), allergic rhinitis(Group 2, AR), atopic dermatitis(Group 3, AD), and chronic urticaria(Group 4, CU). Eighty-seven non-allergic patients (Group 5, NA) included those with pediatric general disorders, except psychomotor retardation, neurologic deficit, malignancy or other chronic disorders. K-CBCL which was filled in by parents or guardian, included eight dimensions of problem behavior: withdrawal, somatic problems, anxiety/ depression, social problems, thought problems, attention problems, delinquent behavior, and aggressive behavior. The first three scales were classified as an Internalizing broadband group and the last two scales as Externalizing group. In addition, the questionnaire included social scale, school scale, and total competence scale. RESULTS: There were no significant differences in age, sex, social economic status between 5 subgroups of allergic and non-allergic patients(p>0.05). The mean problem behavior scores tended to be higher in allergic patient group, but no statistical significance was noted(p>0.05). The mean school scale, social scale, total competence scale of allergic patient group were not significantly higher than those of non-allergic patient group(p>0.05). Combined disease group with more than 2 allergic disorders showed problem behaviors compared to non-allergic group or asthma only group. Total social competence scale was lower in allergic patient group with 1-3 years of disease duration than for shorter(less than 1 year) and longer(more than 3 years) durations. CONCLUSION: Taken together, combined disease group and allergic disease group with 1-3 years of duration showed more problem behaviors and the lowest total social competence scales, respectively.

The Significance of Buckwheat Chaff Stuffed Pillow on the Sensitization to Buckwheat in Asthmatic Children / 소아알레르기및호흡기학회지

PURPOSE: Buckwheat flour (BF) is known as a potent food allergen. Its sensitization usually occurs by ingestion, but also by inhalation due to occupational or domestic exposure. We underwent this study to identify an effect of buckwheat chaff stuffed pillow (BCP) exposure on sensitization to BF and clinical BF allergy in asthmatic children. METHOD: We obtained detailed history of BCP exposure in 36 asthmatic children (aged 0.7-14.2 years). We also performed RIA for specific IgE, BCP-elimination-provocation test. All subjects were divided into 3 groups, Group I (continuous BCP exposurers, n=13), Group II (previous exposurers, n=11), and Group III (non-exposurers to BCP, n=12) and all subjects had no history of ingestion of BF containing foods. RESULTS: In the 13 Group I cases, the durations of BCP exposure were 1-6 years, and 8 of them were users of BCP themselves, 5 were indirect exposurers by family members' BCP. The positive rates of BF specific IgE were 92.3, 36.4% and 8.3% in the Group I, II and III, respectively (Chi-square test, P<0.05). While the positive rates of house dust mites specific IgE were not significantly different among three groups. Twelve out of 13 Group I cases sensitized to BF, and 9 of those 12 were not sensitized to house dust mites. Eight out of 13 Group I cases were positive in BCP elimination-provocation test, during 6-24 month follow-up periods, 7 of them were managed effectively by BCP elimination only. CONCLUSION: Taken together, a small amount of BF attached to BCP can induce BF sensitization and BCP can be a major cause of childhood nocturnal asthma.

A Study on the Cross-allergenicity between Buckwheat and Rice Flour Using IgE-immunoblot Inhibition and ELISA-inhibition Test / 소아알레르기및호흡기학회지

PURPOSE: Buckwheat is one of the potent allergenic foods, whereas rice is considered as the safest and hypoallergenic food in Korea. However rice can be a causative food allergen, and several report about allergic reactions to rice in Japan. And it is partially true that there is some cross-allergenicity among cereal allergens such as buckwheat, barley, wheat, rice. So, we should consider a false positive reaction to rice during allergic skin tests, especially in cereal allergic patients. We found that a part of buckwheat allergic children showed positive skin reactions to rice antigens, without any allergic reactions after rice ingestion. Therefore the positive skin test results to rice were considered as the false positive reactions due to cross-allergenicity with buckwheat allergen. To evaluate this possibility, we undertook this study. METHODS: To evaluate the cross-allergenicity between rice and buckwheat antigens. With the buckwheat sensitive sera and crude extracts of buckwheat flour and rice flour obtained in Korea, we carried out SDS-PAGE analysis, IgE immunoblot, IgE-immouoblot inhibition test and ELISA inhibition test. RESULTS: Buckwheat extract showed more than 13 antigenic bands and rice extract showed more than 9 bands by SDS-PAGE analysis. IgE immunoblot revealed at least 20 IgE-binding components (ranged 120-4 kDa) with buckwheat extract. IgE-binding capacity of 22 kDa buckwheat component was markedly inhibited by rice extract and 8 kDa component was inhibited slightly. Using IgE ELISA inhibition test, we confirmed buckwheat IgE-ELISA was profoundly inhibited by rice extract, and 50% inhibition was shown in 10-100 ug/ml concentration of rice extract. CONCLUSION: Taken together, the positive reactions to rice antigen would be shown by the result of cross-allergenicity of rice with buckwheat antigen.

Immunoblot Analysis of Allergens in Mosquito, Culex pipiens / 소아알레르기및호흡기학회지

PURPOSE: Adverse reactions to mosquito bites have been recognized for some time, and these usually consist of large swellings, generalized urticaria, angioedema, and less frequently asthma. There have been some efforts to define immunologic characteristics of mosquito allergens throughout the world. But, in Korea, the immunologic analysis of mosquito allergen have not been made. METHODS: Extracts of locally distributed female mosquito Culex pipiens, were prepared from their heads and thoraxes. By sodium dodecylsulfate-polyacrylamide gel electrophoresis, proteins of two extracts were isolated. Then their proein bands were transferred to nitrocellulose membrane. Immunoblotting was performed with sera of allergic patients to mosquito bites, then completed by antibodies to human IgE. RESULTS: Immunoblotting showed IgE binding proteins weighing 70 kD, 60 kD, 34 kD in Culex pipiens. CONCLUSION: We found that mosquito antigens induced IgE response, and it suggested that species-specific antigens exist. Further investigation using salivary gland extracts from Culex genus are needed in identifying specific allergens.

Pollen Allergy in Children (ll): The Significance of Tree Pollen As a Causative Allergen in Children with Allergic Diseases

PURPOSE: The positive rates of allergy skin test of pollens are relatively higher in children in Suwon compared to other areas in Korea. To evaluate the significance of tree pollen as a causative allergen, we undertook this study. METHODS: In 252 children with asthma, scratch tests were done with 72 extracts, including 9 tree pollen. Antigen specific serum IgE antibodies were measured by radioimmunoassay. In 2 children, birch-bronchial challenges were performed. RESULTS: By allergic skin tests, 231 of 252 children showed positive skin reactions to more than 1 antigen, and 102 (44.2%) showed positive reactions to tree pollen extracts. Twenty-five (24.5%) were house dust mites non-sensitive, tree pollen sensitive children. The skin test positivity to individual antigens are as follows : D. pteronyssinus (72.7%), D. farinae (68.4%), hazel (53%), willow (53%), birch (19.9%), oak (19.5%), beech (17.3%), alder (10.4%), ash (8.7%) and elm (7.4%). The degree of skin reaction to tree pollen was relatively weaker than those of house dust mites. The positive concordance rates between skin tests and specific IgE reactions to D. pteronyssinus, D. farinae and tree pollens were 94.4%, 77.3% and 64.1%, respectively. Seven out of 25 mite non-sensitive children had seasonal pollinosis and 2 children experienced early asthmatic responses due to birch-bronchial challenge tests. CONCLUSION: Up to 44.2% of children with respiratory allergy showed positive reactions to tree pollen extracts and 24.5% of them were house dust mites non-sensitive cases. Therefore, tree pollen should be investigated as a causative allergen, regardless of a patient's age.

Molecular biological diagnosis of Spinal Muscular atrophy

Spinal muscular atrophy(SMA) is the second most common fatal disease of childhood with autosomal dominant mode of inheritance, and in its less severe form the third most common neuromuscular disease of childhood after Duchenne muscular dystrophy. The genetic defect was found to be on the long arm of chromosome 5(5q11.2-q13.3) where many genes and microsatellite markers were missing. One of the most important genes is the Survival Motor Neuron(SMN) gene which is homozygously missing in 90% of SMA patients. Another important gene, the Neuronal Apoptosis Inhibitory Protein(NAIP) gene was found to be defective in 67% of SMA type I patients. Studies so far suggest SMA occurs when the genes on the long arm of chromosome 5 are mutated or deleted. Recently our hospital encountered 2 SMA patients of type I and II respectively. These patients both had homozygously defective SMN genes but intact NAIP genes. We are reporting these cases with bibliographic review and discussion. Korean SMA patients presumably have defects in SMN genes similar to those found in European patients, although the siginificance of NAIP genes remains to be established. SMN gene defects can be easily diagnosed using PCR and restriction enzymes, and this method could be applied towards convenient prenatal diagnosis and towards screening for family members at risk.