| 1. |
- Ceder, Hannah, et al.
(författare)
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Clinicopathological Factors Associated with Incomplete Excision of High-risk Basal Cell Carcinoma
- 2021
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 101
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Tidskriftsartikel (refereegranskat)abstract
- Research has shown higher rates of incomplete excision among high-risk than low-risk basal cell carcinomas, but data is limited. A single-centre, retrospective study including excised high-risk basal cell carcinomas (type II-III according to the Swedish classification) was performed to determine incomplete excision rates and associated clinicopathological risk factors. Overall, 987 consecutive cases were included. Of these, 203 (20.6%) were incompletely excised. Incomplete excision rates were higher for type III basal cell carcinomas (27.0% vs 17.6% for type II, p < 0.001) and localization on the face and scalp (22.4% vs 14.7% for other locations, p = 0.009), especially on the nose, ear, scalp and periorbital area (28.0-37.0% vs 9.5-16.9% for other locations, p < 0.0001). Circular excisions were also more often incomplete (28.5%) compared with elliptical excisions (17.7%) (p < 0.001). No association was found between incomplete excision rates and tumour size, excision margins, use of a pre-operative biopsy or surgeon experience. Mohs micrographic surgery should be used more often for type II-III basal cell carcinomas on the face and scalp.
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| 2. |
- Ceder, Hannah, et al.
(författare)
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Evaluation of electrical impedance spectroscopy as an adjunct to dermoscopy in short-term monitoring of atypical melanocytic lesions.
- 2016
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Ingår i: Dermatology practical & conceptual. - : Mattioli1885. - 2160-9381. ; 6:4, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Early detection of melanoma is vital for treatment outcome and survival. Short-term sequential digital dermoscopic monitoring (ST-SDDM) involves the capture and assessment of dermoscopic images of one or more atypical melanocytic lesions (AMLs), at baseline and after four months, in order to detect early morphologic changes. Electrical impedance spectroscopy (EIS) is a diagnostic tool with high sensitivity for the detection of malignant melanocytic lesions.The aim of this study was to assess whether EIS, in addition to ST-SDDM, could improve the selection of AMLs requiring surgery.In this retrospective descriptive study, 22 AMLs in 19 patients were monitored with both ST-SDDM and EIS. A modified EIS decision-making algorithm was established. AMLs were excised if any dermoscopic changes were seen and/or if the EIS score had increased significantly at follow-up. Statistical analyses were made including sensitivity, specificity, PPV and NPV.A total of seven lesions (32%) were excised. Four lesions (57%) were excised solely because of dermoscopic changes including a 0.4 mm-thick melanoma and three benign nevi. Three benign lesions (43%) were excised because of increased EIS scores without any dermoscopic changes. The EIS scores at follow-up showed high variability as compared to the initial scores.The addition of EIS to ST-SDDM did not identify additional malignant lesions. There was no correlation between dermoscopic changes seen with ST-SDDM and increased EIS scores. Three histopathologically benign lesions were needlessly excised. Moreover, the low reproducibility and the possible interoperator variability of the method raised concerns.
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| 3. |
- Ceder, Hannah, et al.
(författare)
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Mohs Micrographic Surgery for Primary Versus Recurrent or Incompletely Excised Facial High-risk Basal Cell Carcinomas.
- 2021
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Ingår i: Acta dermato-venereologica. - : Medical Journals Sweden AB. - 1651-2057. ; 101:1
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Tidskriftsartikel (refereegranskat)abstract
- Facial high-risk basal cell carcinomas are preferably treated with Mohs micrographic surgery, but only 10% of patients are offered Mohs micrographic surgery in Sweden. The aim of this retrospective study was to examine the differences between primary and recurrent or incompletely excised facial high-risk basal cell carcinomas undergoing Mohs micrographic surgery, with regard to the number of stages, final defect sizes, reconstructive techniques and other consequences. The study was performed during the period 2012 to 2019 at our centre. A total of 903 basal cell carcinomas in 813 patients (70.1% primary, 10.4% incompletely excised and 19.5% recurrences) were included. The mean number of Mohs micrographic surgery stages was significantly lower for primary basal cell carcinomas compared with recurrences (p=0.03), and the mean final defect size was significantly smaller in primary basal cell carcinomas compared with both recurrent (p<0.0001) and incompletely excised (p=0.003) tumours. Primary basal cell carcinomas tended to more often be reconstructed by primary closure (p=0.08). Mohs micrographic surgery indications for facial high-risk basal cell carcinomas should be respected and used more frequently on primary basal cell carcinomas, in order to enable better utilization of resources and lesimproved outcomes for the patient.
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| 4. |
- Ceder, Mikaela M., et al.
(författare)
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The glycine receptor alpha 3 subunit mRNA expression shows sex-dependent differences in the adult mouse brain
- 2023
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Ingår i: BMC Neuroscience. - : Springer Nature. - 1471-2202. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The glycinergic system plays an important inhibitory role in the mouse central nervous system, where glycine controls the excitability of spinal itch- and pain-mediating neurons. Impairments of the glycine receptors can cause motor and sensory deficits. Glycine exerts inhibition through interaction with ligand-gated ion channels composed of alpha and beta subunits. We have investigated the mRNA expression of the glycine receptor alpha 3 (Glra3) subunit in the nervous system as well as in several peripheral organs of female and male mice.Results Single-cell RNA sequencing (scRNA-seq) data analysis on the Zeisel et al. (2018) dataset indicated widespread but low expression of Glra3 in vesicular glutamate transporter 2 (Vglut2, Slc17a6) positive and vesicular inhibitory amino acid transporter (Viaat, Slc32a1)positive neurons of the mouse central nervous system. Highest occurrence of Glra3 expression was identified in the cortex, amygdala, and striatal regions, as well as in the hypothalamus, brainstem and spinal cord. Bulk quantitative real-time-PCR (qRT-PCR) analysis demonstrated Glra3 expression in cortex, amygdala, striatum, hypothalamus, thalamus, pituitary gland, hippocampus, cerebellum, brainstem, and spinal cord. Additionally, male mice expressed higher levels of Glra3 in all investigated brain areas compared with female mice. Lastly, RNAscope spatially validated Glra3 expression in the areas indicated by the single-cell and bulk analyses. Moreover, RNAscope analysis confirmed co-localization of Glra3 with Slc17a6 or Slc32a1 in the central nervous system areas suggested from the single-cell data.Conclusions Glra3 expression is low but widespread in the mouse central nervous system. Clear sex-dependent differences have been identified, indicating higher levels of Glra3 in several telencephalic and diencephalic areas, as well as in cerebellum and brainstem, in male mice compared with female mice.
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| 5. |
- Franck, Marina Christina Mikaela, et al.
(författare)
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Urocortin3-expressing neurons in sensory transmission
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Urocortin 3 (UCN3) is a neuropeptide involved in mechanosensation and stress regulation, and Ucn3-Cre neurons have been assigned a role in mechanical itch. Here, we show that Ucn3 marks a population of excitatory neurons in the mouse dorsal horn, divided into two non-overlapping subpopulations expressing protein kinase C g or calretinin/calbindin 2. Chemogenetic activation of spinal Ucn3-Cre neurons evoked a targeted biting/licking behavior towards the corresponding dermatome. Genetic deletion of vesicular glutamate transporter 2 (VGLUT2) in Ucn3-Cre neurons removed the phenotype, showing that the biting/licking behavior is VGLUT2-dependent. Conditional deletion of VGLUT2 did not affect acute thermal or mechanical withdrawal responses, nor thermal withdrawal responses after nerve growth factor-induced hypersensitivity or the prurifensive response to 48/80 or von Frey stimuli applied in nape. Instead, we found that a group of spinal Ucn3 neurons were activated in response to artificial scratching or 48/80-induced itch. Electrophysiological experiments showed that spinal Ucn3 neurons received both glycinergic and GABAergic tonic inhibition, and monosynaptic inputs from both Aβ and C fibers, which could be confirmed by rabies tracing. Spinal Ucn3/Ucn3-Cre neurons thus represent a mechanically sensitive population with several roles in the itch-scratch cycle.
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| 6. |
- Polesie, Sam, et al.
(författare)
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Can Dermoscopy Be Used to Predict if a Melanoma Is In Situ or Invasive?
- 2021
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Ingår i: Dermatology Practical & Conceptual. - : Mattioli1885. - 2160-9381. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: The preoperative prediction of whether melanomas are invasive or in situ can influence initial management. Objectives: This study evaluated the accuracy rate, interobserver concordance, sensitivity and specificity in determining if a melanoma is invasive or in situ, as well as the ability to predict invasive melanoma thickness based on clinical and dermoscopic images. Methods: In this retrospective, single-center investigation, 7 dermatologists independently reviewed clinical and dermoscopic images of melanomas to predict if they were invasive or in situ and, if invasive, their Breslow thickness. Fleiss' and Cohen's kappa (kappa) were used for interobserver concordance and agreement with histopathological diagnosis. Results: We included 184 melanomas (110 invasive and 74 in situ). Diagnostic accuracy ranged from 67.4% to 76.1%. Accuracy rates for in situ and invasive melanomas were 57.5% (95% confidence interval [I], 53.1%-61.8%) and 81.7% (95% CI, 78.8%-84.4%), respectively. Interobserver concordance was moderate (kappa = 0.47; 95% CI, 0.44-0.51). Sensitivity for predicting invasiveness ranged from 63.6% to 91.8% for 7 observers, while specificity was 32.4%-82.4%. For all correctly predicted invasive melanomas, agreement between predictions and correct thickness over or under 1.0 mm was moderate (kappa = 0.52; 95% CI, 0.45-0.58). All invasive melanomas incorrectly predicted by any observer as in situ had a thickness <1.0 mm. All 32 melanomas >1.0 mm were correctly predicted to be invasive by all observers. Conclusions: Accuracy rates for predicting thick melanomas were excellent, melanomas inaccurately predicted as in situ were all thin, and interobserver concordance for predicting in situ or invasive melanomas was moderate. Preoperative dermoscopy of suspected melanomas is recommended for choosing appropriate surgical margins.
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| 7. |
- Polesie, Sam, et al.
(författare)
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Discrimination Between Invasive and In Situ Melanomas Using Clinical Close-Up Images and a De Novo Convolutional Neural Network
- 2021
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Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Melanomas are often easy to recognize clinically but determining whether a melanoma is in situ (MIS) or invasive is often more challenging even with the aid of dermoscopy. Recently, convolutional neural networks (CNNs) have made significant and rapid advances within dermatology image analysis. The aims of this investigation were to create a de novo CNN for differentiating between MIS and invasive melanomas based on clinical close-up images and to compare its performance on a test set to seven dermatologists. Methods: A retrospective study including clinical images of MIS and invasive melanomas obtained from our department during a five-year time period (2016-2020) was conducted. Overall, 1,551 images [819 MIS (52.8%) and 732 invasive melanomas (47.2%)] were available. The images were randomized into three groups: training set (n = 1,051), validation set (n = 200), and test set (n = 300). A de novo CNN model with seven convolutional layers and a single dense layer was developed. Results: The area under the curve was 0.72 for the CNN (95% CI 0.66-0.78) and 0.81 for dermatologists (95% CI 0.76-0.86) (P < 0.001). The CNN correctly classified 208 out of 300 lesions (69.3%) whereas the corresponding number for dermatologists was 216 (72.0%). When comparing the CNN performance to each individual reader, three dermatologists significantly outperformed the CNN. Conclusions: For this classification problem, the CNN was outperformed by the dermatologist. However, since the algorithm was only trained and validated on 1,251 images, future refinement and development could make it useful for dermatologists in a real-world setting.
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| 8. |
- Polesie, Sam, et al.
(författare)
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Interobserver Agreement on Dermoscopic Features and their Associations with In Situ and Invasive Cutaneous Melanomas.
- 2021
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Ingår i: Acta dermato-venereologica. - : Medical Journals Sweden AB. - 1651-2057 .- 0001-5555. ; 101:10
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Tidskriftsartikel (refereegranskat)abstract
- Several melanoma-specific dermoscopic features have been described, some of which have been reported as indicative of in situ or invasive melanomas. To assess the usefulness of these features to differentiate between these 2 categories, a retrospective, single-centre investigation was conducted. Dermoscopic images of melanomas were reviewed by 7 independent dermatologists. Fleiss' kappa (κ) was used to analyse interobserver agreement of predefined features. Logistic regression and odds ratios were used to assess whether specific features correlated with melanoma in situ or invasive melanoma. Overall, 182 melanomas (101 melanoma in situ and 81 invasive melanomas) were included. The interobserver agreement for melanoma-specific features ranged from slight to substantial. Atypical blue-white structures (κ=0.62, 95% confidence interval 0.59-0.65) and shiny white lines (κ=0.61, 95% confidence interval 0.58-0.64) had a substantial interobserver agreement. These 2 features were also indicative of invasive melanomas >1.0 mm in Breslow thickness. Furthermore, regression/peppering correlated with thin invasive melanomas. The overall agreement for classification of the lesions as invasive or melanoma in situ was moderate (κ=0.52, 95% confidence interval 0.49-0.56).
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| 9. |
- Weman, Hannah M., 1993-, et al.
(författare)
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Spinal glycine receptor alpha 3 subunit-expressing cells transmit the sensations of compound 48/80 and chloroquine
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Glycinergic neurons regulate nociceptive and pruriceptive signaling in the spinal cord, but the identity and role of the glycine-regulated neurons are not fully known. Herein, we have characterized spinal glycine receptor alpha 3 (Glra3) subunit-expressing neurons in a Glra3-Cre mouse line. Glra3-Cre neurons express Glra3, are located mainly in laminae III-VI and respond to glycine. Chemogenetic activation of spinal Glra3-Cre neurons induced biting/licking, stamping and guarding behaviors, while inhibition reduced behaviors evoked by compound 48/80 and chloroquine, revealing a pruriceptive role for this population. Spinal cells activated by compound 48/80 or chloroquine express Glra3, further supporting the phenotype. Retrograde tracing revealed that spinal Glra3-Cre neurons receive input mainly from NF200(+), IB4(+), TRKA(+), CGRP(+) or SST(+) primary afferents. Dorsal root stimulation validated the monosynaptic input from primary afferents, which was mainly comprised of C-fiber or C-fiber and Aα∕β input. Conclusively, these results show that spinal Glra3 neurons contribute to acute transmission of compound 48/80 and chloroquine-induced itch.
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