Augmented decision-making for acral lentiginous melanoma detection using deep convolutional neural networks.

BACKGROUND: Several studies have achieved high-level performance of melanoma detection using convolutional neural networks (CNNs). However, few have described the extent to which the implementation of CNNs improves the diagnostic performance of the physicians. OBJECTIVE: This study is aimed at developing a CNN for detecting acral lentiginous melanoma (ALM) and investigating whether its implementation can improve the initial decision for ALM detection made by the physicians. METHODS: A CNN was trained using 1072 dermoscopic images of acral benign nevi, ALM and intermediate tumours. To investigate whether the implementation of CNN can improve the initial decision for ALM detection, 60 physicians completed a three-stage survey. In Stage I, they were asked for their decisions solely on the basis of dermoscopic images provided to them. In Stage II, they were also provided with clinical information. In Stage III, they were provided with the additional diagnosis and probability predicted by the CNN. RESULTS: The accuracy of ALM detection in the participants was 74.7% (95% confidence interval [CI], 72.6-76.8%) in Stage I and 79.0% (95% CI, 76.7-81.2%) in Stage II. In Stage III, it was 86.9% (95% CI, 85.3-88.4%), which exceeds the accuracy delivered in Stage I by 12.2%p (95% CI, 10.1-14.3%p) and Stage II by 7.9%p (95% CI, 6.0-9.9%p). Moreover, the concordance between the participants considerably increased (Fleiss-κ of 0.436 [95% CI, 0.437-0.573] in Stage I, 0.506 [95% CI, 0.621-0.749] in Stage II and 0.684 [95% CI, 0.621-0.749] in Stage III). CONCLUSIONS: Augmented decision-making improved the performance of and concordance between the clinical decisions of a diverse group of experts. This study demonstrates the potential use of CNNs as an adjoining, decision-supporting system for physicians' decisions.

Stratum corneum occlusion induces water transformation towards lower bonding state: a molecular level in vivo study by confocal Raman microspectroscopy.

OBJECTIVE: It is conventionally understood that occlusive effects are the retention of excessive water in the stratum corneum (SC), the increase of SC thickness (swelling) and a decrease of the transepidermal water loss. However, the influence of occlusion on water binding properties in the SC is unknown. METHODS: The action of plant-derived jojoba and almond oils, as well as mineral-derived paraffin oil and petrolatum topically applied on human skin, is investigated in vivo using confocal Raman microspectroscopy. To understand the oils' influence on the SC on the molecular level, the depth-dependent hydrogen bonding states of water in the SC and their relationship to the conformation of keratin, concentration of natural moisturizing factor (NMF) molecules and lipid organization were investigated. RESULTS: A significant SC swelling was observed only in petrolatum-treated skin. The water concentration was increased in oil-treated skin in the intermediate SC region (40-70% SC depth). Meanwhile, the amount of free, weakly and tightly bound water increased, and strongly bound water decreased in the uppermost SC region (0-30% SC depth). The NMF concentration of oil-treated skin was significantly lower at 50-70% SC depth. The lateral organization of lipids in oil-treated skin was lower at 0-30% SC depth. The secondary structure of keratin was changed towards an increase of ß-sheet content in mineral-derived oil-treated skin and changed towards an increase of α-helix content in plant-derived oil-treated skin. CONCLUSION: The occlusive properties can be summarized as the increase of free water and the transformation of water from a more strongly to a more weakly hydrogen bonding state in the uppermost SC, although some oils cause insignificant changes of the SC thickness. The accompanied changes in the keratin conformation at the intermediate swelling region of the SC also emphasize the role of keratin in the SC's water-transporting system, that is the water in the SC transports intercellularly and intracellularly in the intermediate swelling region and only intercellularly in the uppermost non-swelling region. Bearing this in mind, almond, jojoba and paraffin oils, which are not occlusive from the conventional viewpoint, have an occlusion effect similar to petrolatum on the SC.

OBJECTIF: Il est généralement entendu que les effets occlusifs consistent en la rétention d'un excès d'eau dans la couche cornée (stratum corneum, SC), l'augmentation d'épaisseur de la SC (gonflement) et une diminution de la perte d'eau trans-épidermique. Cependant, l'influence de l'occlusion sur les propriétés de fixation de l'eau dans le SC est inconnue. MÉTHODES: L'action des huiles de jojoba et d'amande d'origine végétale, ainsi que des huiles de paraffine et de pétrolatum d'origine minérale appliquées topiquement sur la peau humaine est étudiée in vivo à l'aide de la microspectroscopie Raman confocale. Pour comprendre l'influence des huiles sur le SC au niveau moléculaire, on a étudié les états de liaison hydrogène de l'eau dans le SC en fonction de la profondeur et leur relation avec la conformation de la kératine, la concentration des molécules du facteur naturel d'hydratation (NMF) et l'organisation des lipides. RÉSULTATS: Un gonflement significatif de le SC n'a été observé que dans la peau traitée au pétrolatum. La concentration en eau a été augmentée dans la peau traitée au pétrolatum dans la région SC intermédiaire (40-70% de profondeur du SC). En meme temps, la quantité d'eau libre, faiblement et fortement liée augmentait, tandis que l'eau fortement liée diminuait dans la région SC supérieure (0-30% de profondeur du SC). La concentration en NMF de la peau traitée à l'huile était plus basse d´une manière significative à 50-70% de profondeur du SC. L'organisation latérale des lipides dans la peau huilée était plus basse à une profondeur du SC de 0 à 30 %. La structure secondaire de la kératine a été modifiée pour augmenter la teneur en feuillet-ß dans les peaux huilées d'origine minérale et pour augmenter la teneur en hélice α dans les peaux huilées d'origine végétale. CONCLUSION: Les propriétés occlusives peuvent être résumées comme l'augmentation de l'eau libre et la transformation de l'eau d'un état de liaison hydrogène plus fort à un état de liaison hydrogène plus faible dans le SC supérieure, bien que certaines huiles provoquent des changements insignifiants de l'épaisseur de la SC. Les modifications de la conformation de la kératine dans la zone de gonflement intermédiaire du SC soulignent également le rôle de la kératine dans le système de transport de l'eau du SC, c'est-à-dire que l'eau est transportée du SC de manière intercellulaire et intracellulaire dans la zone de gonflement intermédiaire et seulement de manière intercellulaire dans la zone non gonflée la plus élevée. En considérant cela, les huiles d'amande, de jojoba et de paraffine, qui ne sont pas occlusives du point de vue conventionnel, ont un effet d'occlusion similaire à celui du pétrolatum sur le SC.

Association between ambient air pollution and pregnancy rate in women who underwent IVF.

STUDY QUESTION: Are the concentrations of five criteria air pollutants associated with probabilities of biochemical pregnancy loss and intrauterine pregnancy in women? SUMMARY ANSWER: Increased concentrations of ambient particulate matter (PM10), nitrogen dioxide (NO2), carbon monoxide (CO) during controlled ovarian stimulation (COS) and after embryo transfer were associated with a decreased probability of intrauterine pregnancy. WHAT IS KNOWN ALREADY: Exposure to high ambient air pollution was suggested to be associated with low fertility and high early pregnancy loss in women. STUDY DESIGN, SIZE, DURATION: Using a retrospective cohort study design, we analysed 6621 cycles of 4581 patients who underwent one or more fresh IVF cycles at a fertility centre from January 2006 to December 2014, and lived in Seoul at the time of IVF treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS: To estimate patients' individual exposure to air pollution, we computed averages of hourly concentrations of five air pollutants including PM10, NO2, CO, sulphur dioxide (SO2) and ozone (O3) measured at 40 regulatory monitoring sites in Seoul for each of the four exposure periods: period 1 (start of COS to oocyte retrieval), period 2 (oocyte retrieval to embryo transfer), period 3 (embryo transfer to hCG test), and period 4 (start of COS to hCG test). Hazard ratios (HRs) from the time-varying Cox-proportional hazards model were used to estimate probabilities of biochemical pregnancy loss and intrauterine pregnancy for an interquartile range (IQR) increase in each air pollutant concentration during each period, after adjusting for individual characteristics. We tested the robustness of the result using generalised linear mixed model, accounting for within-woman correlation. MAIN RESULTS AND THE ROLE OF CHANCE: Mean age of the women was 35 years. Average BMI was 20.9 kg/m2 and the study population underwent 1.4 IVF cycles on average. Cumulative pregnancy rate in multiple IVF cycles was 51.3% per person. Survival analysis showed that air pollution during periods 1 and 3 was generally associated with IVF outcomes. Increased NO2 (adjusted HR = 0.93, 95% CI: 0.87, 0.99) and CO (0.94, 95% CI: 0.89, 1.00) during period 1 were associated with decreased probability of intrauterine pregnancy. PM10 (0.92, 95% CI: 0.85, 0.99), NO2 (0.93, 95% CI = 0.86, 1.00) and CO (0.93, 95% CI: 0.87, 1.00) levels during period 3 were also inversely associated with intrauterine pregnancy. Both PM10 (1.17, 95% CI: 1.04 1.33) and NO2 (1.18, 95% CI: 1.03, 1.34) during period 3 showed positive associations with biochemical pregnancy loss. LIMITATIONS, REASONS FOR CAUTION: The district-specific ambient air pollution treated as an individual exposure may not represent the actual level of each woman's exposure to air pollution. Smoking, working status, parity or gravidity of women, and semen analysis data were not included in the analysis. WIDER IMPLICATIONS OF THE FINDINGS: This study provided evidence of an association between increased ambient concentrations of PM10, NO2 and CO and reduced probabilities for achieving intrauterine pregnancy using multiple IVF cycle data. Specifically, our results indicated that lower intrauterine pregnancy rates in IVF cycles may be linked to ambient air pollution during COS and the post-transfer period. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2013 R1A6A3A04059017, 2016 R1D1A1B03933410 and 2018 R1A2B6004608) and the National Cancer Center of Korea (NCC-1810220-01). The authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Impact of TGF-ß family-related growth factors on chondrogenic differentiation of adipose-derived stem cells isolated from lipoaspirates and infrapatellar fat pads of osteoarthritic patients.

The success of cell-based approaches for the treatment of cartilage defects requires an optimal autologous cell source with chondrogenic differentiation ability that maintains its differentiated properties and stability following implantation. The objective of this study was to compare the chondrogenic capacity of mesenchymal stem cells (MSCs) isolated from lipoaspirates (ASCs) and the infrapatellar fat pad (IFPSCs) of osteoarthritic patients and treated with transforming growth factor (TGF)-ß family-related growth factors. Cells were cultured for 6 weeks in a 3D pellet culture system with the chimeric activin A/bone morphogenic protein (BMP)-2 ligand (AB235), the chimeric nodal/BMP-2 ligand (NB260) or BMP-2. To investigate the stability of the new cartilage, ASCs-treated pellets were transplanted subcutaneously into severe combined immunodeficiency (SCID) mice. Histological and immunohistochemical assessment confirmed that the growth factors induced cartilage differentiation in both isolated cell types. However, reverse transcription-quantitative PCR results showed that ASCs presented a higher chondrogenic potential than IFPSCs. In vivo results revealed that AB235-treated ASCs pellets were larger in size and could form stable cartilage-like tissue as compared to NB260-treated pellets, while BMP-2-treated pellets underwent calcification. The chondrogenic induction of ASCs by AB235 treatment was mediated by SMAD2/3 activation, as proved by immunofluorescence analysis. The results of this study indicated that the combination of ASCs and AB235 might lead to a cell-based cartilage regeneration treatment.

Effects of ß-Glucan on the Release of Nitric Oxide by Macrophages Stimulated with Lipopolysaccharide.

This research analyzed the effect of ß-glucan that is expected to alleviate the production of the inflammatory mediator in macrophagocytes, which are processed by the lipopolysaccharide (LPS) of Escherichia. The incubated layer was used for a nitric oxide (NO) analysis. The DNA-binding activation of the small unit of nuclear factor-κB was measured using the enzyme-linked immunosorbent assay-based kit. In the RAW264.7 cells that were vitalized by Escherichia coli (E. coli) LPS, the ß-glucan inhibited both the combatant and rendering phases of the inducible NO synthase (iNOS)-derived NO. ß-Glucan increased the expression of the heme oxygenase-1 (HO-1) in the cells that were stimulated by E. coli LPS, and the HO-1 activation was inhibited by the tin protoporphyrin IX (SnPP). This shows that the NO production induced by LPS is related to the inhibition effect of ß-glucan. The phosphorylation of c-Jun N-terminal kinases (JNK) and the p38 induced by the LPS were not influenced by the ß-glucan, and the inhibitory κB-α (IκB-α) decomposition was not influenced either. Instead, ß-glucan remarkably inhibited the phosphorylation of the signal transducer and activator of transcription-1 (STAT1) that was induced by the E. coli LPS. Overall, the ß-glucan inhibited the production of NO in macrophagocytes that was vitalized by the E .coli LPS through the HO-1 induction and the STAT1 pathways inhibition in this research. As the host immune response control by ß-glucan weakens the progress of the inflammatory disease, ß-glucan can be used as an effective immunomodulator.

Effect of caffeic acid phenethyl ester on Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.

BACKGROUND AND OBJECTIVE: Caffeic acid phenethyl ester (CAPE) has numerous potentially beneficial properties, including antioxidant, immunomodulatory and anti-inflammatory activities. However, the effect of CAPE on periodontal disease has not been studied before. This study was designed to investigate the efficacy of CAPE in ameliorating the production of proinflammatory mediators in macrophages activated by lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in periodontal disease. MATERIAL AND METHODS: LPS from P. intermedia ATCC 25611 was isolated by using the standard hot phenol-water method. Culture supernatants were assayed for nitric oxide (NO), interleukin (IL)-1ß and IL-6. We used real-time polymerase chain reaction to quantify inducible NO synthase, IL-1ß, IL-6, heme oxygenase (HO)-1 and suppressors of cytokine signaling (SOCS) 1 mRNA expression. HO-1 protein expression and levels of signaling proteins were assessed by immunoblot analysis. DNA-binding activities of NF-κB subunits were analyzed by using the enzyme-linked immunosorbent assay-based kits. RESULTS: CAPE exerted significant inhibitory effects on P. intermedia LPS-induced production of NO, IL-1ß and IL-6 as well as their mRNA expression in RAW264.7 cells. CAPE-induced HO-1 expression in cells activated with P. intermedia LPS, and selective inhibition of HO-1 activity by tin protoporphyrin IX attenuated the inhibitory effect of CAPE on LPS-induced NO production. CAPE did not interfere with IκB-α degradation induced by P. intermedia LPS. Instead, CAPE decreased nuclear translocation of NF-κB p65 and p50 subunits induced with LPS, and lessened LPS-induced p50 binding activity. Further, CAPE showed strong inhibitory effects on LPS-induced signal transducer and activator of transcription 1 and 3 phosphorylation. Besides, CAPE significantly elevated SOCS1 mRNA expression in P. intermedia LPS-stimulated cells. CONCLUSION: Modulation of host response by CAPE may represent an attractive strategy towards the treatment of periodontal disease. In vivo studies are required to appraise the potential of CAPE further as an immunomodulator in the treatment of periodontal disease.

Relaxation dynamics of liposomes in an aqueous solution.

The gel-liquid crystal phase transition has been studied by the temperature and frequency dependent dielectric relaxation behavior of liposomes in an aqueous solution (40 g L(-1) DPPC-water mixture). Four relaxation processes were observed in the frequency range from 40 Hz to 30 GHz which were ascribed to different molecular mechanisms, related to the structural units of the system. The gel-liquid crystal phase transition was also described very accurately from the temperature-dependent dielectric relaxation strength, relaxation time and symmetric shape parameter of the relaxation functions obtained from the fitting procedure. Relaxation process 3, obtained from the dielectric fitting procedure, was confirmed by dielectric modulus analysis. A comparison of the lipid membrane with non-biological systems like liquid crystals was performed. It was determined that the lipid membrane has a ferroelectric liquid crystal like behavior. Process 3 is comparable to the soft mode relaxation process observed in ferroelectric liquid crystals which was detected close to the smectic-C*-smectic-A phase transition. Differential scanning calorimetry was also used to confirm the gel-liquid crystal phase transition of this mixture.

Translational positioning of a magnetic domain wall in ferromagnetic nanowires using a stray field filter.

Understanding the interaction between the magnetic domain wall and the various artificial defects in ferromagnetic nanowires has been of utmost importance for the future realization of the spintronic devices based on the magnetic domain wall motion in nanowires. In this work, the chirality filter effect of the magnetic domain wall in T-shaped ferromagnetic nanowires with a stray field filter was investigated via micromagnetic simulation. A tapered wire was attached to the flat nanowires to form a potential barrier or well for the domain wall propagating along them. For the domain wall passing through the potential barrier or the potential well, the spin structure of the domain wall and the interaction between the domain wall and the potential barrier/well were investigated in detail. The chirality-dependent translational positioning of the domain wall was intensively examined for the potential barrier and potential well cases. The domain wall chirality transmission on relatively long length scales using a series of potential wells was explored.