Hyperspectral Imaging Reveals Spectral Differences and Can Distinguish Malignant Melanoma from Pigmented Basal Cell Carcinomas : A Pilot Study

Pigmented basal cell carcinomas can be difficult to distinguish from melanocytic tumours. Hyperspectral imaging is a non-invasive imaging technique that measures the reflectance spectra of skin in vivo. The aim of this prospective pilot study was to use a convolutional neural network classifier in hyperspectral images for differential diagnosis between pigmented basal cell carcinomas and melanoma. A total of 26 pigmented lesions (10 pigmented basal cell carcinomas, 12 melanomas in situ, 4 invasive melanomas) were imaged with hyperspectral imaging and excised for histopatho-logical diagnosis. For 2-class classifier (melano-cytic tumours vs pigmented basal cell carcinomas) using the majority of the pixels to predict the class of the whole lesion, the results showed a sensitivity of 100% (95% confidence interval 81-100%), specificity of 90% (95% confidence interval 60-98%) and positive predictive value of 94% (95% confidence interval 73-99%). These results indicate that a convolutional neural network classifier can differentiate melanocytic tumours from pigmented basal cell carcinomas in hyperspectral images. Further studies are warranted in order to confirm these preliminary results, using larger samples and multiple tumour types, including all types of melanocytic lesions.Peer reviewe

Risk for colorectal cancer after computed tomography verified acute diverticulitis : A retrospective cohort study with long-term follow-up

Background and objective: Colorectal cancer (CRC) can mimic acute diverticulitis and can thus be misdiagnosed. Therefore, colonic evaluation is recommended after an episode of acute diverticulitis. The aim of this study was to analyze the risk of CRC after computed tomography (CT) verified uncomplicated and complicated acute diverticulitis in short-term and, particularly, long-term follow-up to ensure the feasibility of the primary CT imaging in separating patients with uncomplicated and complicated acute diverticulitis. Methods: A retrospective cohort study was conducted in patients with CT-verified acute diverticulitis in 2003–2012. Data on CT findings and colonic evaluations were analyzed. The patients were divided into those with uncomplicated and complicated acute diverticulitis. Patient charts were reviewed 9–18 years after the initial acute diverticulitis episode. Results: The study population consisted of 270 patients. According to CT scans, 170 (63%) patients had uncomplicated acute diverticulitis and 100 (37%) had complicated acute diverticulitis. Further colonic evaluation was made in 146 (54%) patients. In the whole study population, CRC was found in 7 (2.6%) patients, but CRC was associated with acute diverticulitis in only 4 (1.5%) patients. The short-term risk for CRC was 0.6% (1/170) in uncomplicated acute diverticulitis and 3.0% (3/100) in complicated acute diverticulitis. No additional CRC was found in patients with complicated acute diverticulitis during the long-term follow-up and three cases of CRC found after uncomplicated acute diverticulitis had no observable association with previous diverticulitis. Conclusions: In short-term follow-up, the risk of underlying CRC is very low in CT-verified uncomplicated acute diverticulitis but increased in complicated acute diverticulitis. Long-term follow-up revealed no additional CRCs associated with previous acute diverticulitis, indicating that the short-term results remain consistent also in the long run. These long-term results confirm that colonoscopy should be reserved for patients with complicated acute diverticulitis or with persisting or alarming symptoms.Peer reviewe

Macroscopic appearance of the major duodenal papilla influences bile duct cannulation : a prospective multicenter study by the Scandinavian Association for Digestive Endoscopy Study Group for ERCP

Background and Aims: Certain appearances of the major duodenal papilla have been claimed to make cannulation more difficult during ERCP. This study uses a validated classification of the endoscopic appearance of the major duodenal papilla to determine if certain types of papilla predispose to difficult cannulation. Methods: Patients with a naive papilla scheduled for ERCP were included. The papilla was classified into 1 of 4 papilla types before cannulation started. Time to successful bile duct cannulation, attempts, and number of pancreatic duct passages were recorded. Difficult cannulation was defined as after 5 minutes, 5 attempts, or 2 pancreatic guidewire passages. Results: A total of 1401 patients were included from 9 different centers in the Nordic countries. The overall frequency of difficult cannulation was 42% (95% confidence interval [CI], 39%-44%). Type 2 small papilla (52%; 95% CI, 45%-59%) and type 3 protruding or pendulous papilla (48%; 95% CI, 42%-53%) were more frequently difficult to cannulate compared with type 1 regular papilla (36%; 95% CI, 33%-40%; both P <.001). If an inexperienced endoscopist started cannulation, the frequency of failed cannulation increased from 1.9% to 6.3% (P <.0001), even though they were replaced by a senior endoscopist after 5 minutes. Conclusions: The endoscopic appearance of the major duodenal papilla influences bile duct cannulation. Small type 2 and protruding or pendulous type 3 papillae are more frequently difficult to cannulate. In addition, cannulation might even fail more frequently if a beginner starts cannulation. These findings should be taken into consideration when performing studies regarding bile duct cannulation and in training future generations of endoscopists.Peer reviewe

Narrowband ultraviolet B phototherapy improves quality of life of psoriasis and atopic dermatitis patients up to 3 months : Results from an observational multicenter study

Background/Purpose Narrowband UVB phototherapy is a common treatment modality in psoriasis and atopic dermatitis, but evidence of its actual effect in clinical setting is sparse. Our aim was to assess the effectiveness and costs of narrowband UVB phototherapy in psoriasis and atopic dermatitis in clinical setting. Methods We observed 207 psoriasis patients and 144 atopic dermatitis patients in eight centers. SAPASI, PO-SCORAD, and VAS measures were used at baseline, at the end, and 3 months after the narrowband UVB phototherapy course. Quality of life was measured using Dermatology Life Quality Index (DLQI), and costs were assessed using a questionnaire. Results In both psoriasis and atopic dermatitis, the DLQI and Self-Administrated PASI (SAPASI)/Patient-Oriented SCORAD (PO-SCORAD) improved significantly and the results remained improved for at least 3 months in both groups. Alleviation of pruritus correlated with better quality of life in both patient groups. We reported slight redness and burning side effects which were due to lack of MED testing. Self-administered tools proved to be useful in evaluating pruritus and severity of the disease in psoriasis and atopic dermatitis. Mean patient costs were 310 euro and 21 hours of time, and mean costs for the healthcare provider were 810 euro. Conclusion In psoriasis, narrowband UVB is a very efficient treatment in clinical setting, whereas in atopic dermatitis, more studies are needed to determine the best dosage.Peer reviewe

Ultraviolet B radiation modifies circadian time in epidermal skin and in subcutaneous adipose tissue

Background Recent findings suggest that circadian time regulates cellular functions in the skin and may affect protection against ultraviolet radiation (UVR). It is not known, however, whether UVR through skin directly affects the expression of circadian genes. We investigated the effect of ultraviolet B (UVB) exposure on cryptochrome circadian clock 1 (CRY1), cryptochrome circadian clock 2 (CRY2), and circadian associated repressor of transcription (CIART) genes. Methods Healthy volunteers (n = 12) were exposed to narrow-band UVB radiation of four standard erythemal dose (SED). Epidermal/dermal and subcutaneous adipose tissue samples were obtained by punch biopsies from irradiated and non-irradiated skin 10 cm away from the irradiated site 24 hours after UVB exposure. Gene expression of CRY1, CRY2, and CIART was measured using RT-PCR (TaqMan). Results Ultraviolet B radiation affected mRNA expression in the epidermal/dermal skin and in the subcutaneous adipose tissue. It down-regulated expression of CRY2 gene in the epidermal/dermal skin, whereas it up-regulated expression of CRY1 and CIART genes in the subcutaneous adipose tissue. Conclusion We showed for the first time that UVB radiation affects expression of circadian genes in the subcutaneous adipose tissue. Further studies are warranted to understand the mechanisms in detail.Peer reviewe

A Placebo-controlled double-blinded test of the biodiversity hypothesis of immune-mediated diseases : Environmental microbial diversity elicits changes in cytokines and increase in T regulatory cells in young children

Background: According to the biodiversity hypothesis of immune-mediated diseases, lack of microbiological di-versity in the everyday living environment is a core reason for dysregulation of immune tolerance and - even-tually - the epidemic of immune-mediated diseases in western urban populations. Despite years of intense research, the hypothesis was never tested in a double-blinded and placebo-controlled intervention trial.Objective: We aimed to perform the first placebo-controlled double-blinded test that investigates the effect of biodiversity on immune tolerance. Methods: In the intervention group, children aged 3-5 years were exposed to playground sand enriched with microbially diverse soil, or in the placebo group, visually similar, but microbially poor sand colored with peat (13 participants per treatment group). Children played twice a day for 20 min in the sandbox for 14 days. Sand, skin and gut bacterial, and blood samples were taken at baseline and after 14 days. Bacterial changes were followed for 28 days. Sand, skin and gut metagenome was determined by high throughput sequencing of bacterial 16 S rRNA gene. Cytokines were measured from plasma and the frequency of blood regulatory T cells was defined as a percentage of total CD3 +CD4 + T cells. Results: Bacterial richness (P < 0.001) and diversity (P < 0.05) were higher in the intervention than placebo sand. Skin bacterial community, including Gammaproteobacteria, shifted only in the intervention treatment to resemble the bacterial community in the enriched sand (P < 0.01). Mean change in plasma interleukin-10 (IL-10) concentration and IL-10 to IL-17A ratio supported immunoregulation in the intervention treatment compared to the placebo treatment (P = 0.02). IL-10 levels (P = 0.001) and IL-10 to IL-17A ratio (P = 0.02) were associated with Gammaproteobacterial community on the skin. The change in Treg frequencies was associated with the relative abundance of skin Thermoactinomycetaceae 1 (P = 0.002) and unclassified Alphaproteobacteria (P < 0.001). After 28 days, skin bacterial community still differed in the intervention treatment compared to baseline (P < 0.02). Conclusions: This is the first double-blinded placebo-controlled study to show that daily exposure to microbial biodiversity is associated with immune modulation in humans. The findings support the biodiversity hypothesis of immune-mediated diseases. We conclude that environmental microbiota may contribute to child health, and that adding microbiological diversity to everyday living environment may support immunoregulation.Peer reviewe

Skin, gut, and sand metagenomic data on placebo-controlled sandbox biodiversity intervention study

The metagenomic data presented in this article are related to the published research of "A Placebo-controlled doubleblinded test of the biodiversity hypothesis of immunemediated diseases: Environmental microbial diversity elicits changes in cytokines and increase in T regulatory cells in young children"This database contains 16S ribosomal RNA (rRNA) metagenomics of sandbox sand and skin and gut microbiota of children in the intervention and placebo daycares. In inter-vention daycares, children aged 3-5 years were exposed to playground sand enriched with microbially diverse soil. In placebo daycares, children were exposed to visually similar as in intervention daycares, but microbially poor sand col-ored with peat. Sand, skin and gut metagenomics were an-alyzed at baseline and after 14 and 28 days of interven-tion by high throughput sequencing of bacterial 16S rRNA gene on the Illumina MiSeq platform. This dataset shows how skin bacterial community composition, including classes Gammaproteobacteria and Bacilli, changed, and how the rel-ative abundance of over 30 bacterial genera shifted on the skin of children in the intervention treatment, while no shifts occurred in the placebo group.(c) 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Peer reviewe

Permutation-based significance analysis reduces the type 1 error rate in bisulfite sequencing data analysis of human umbilical cord blood samples

DNA methylation patterns are largely established in-utero and might mediate the impacts of in-utero conditions on later health outcomes. Associations between perinatal DNA methylation marks and pregnancy-related variables, such as maternal age and gestational weight gain, have been earlier studied with methylation microarrays, which typically cover less than 2% of human CpG sites. To detect such associations outside these regions, we chose the bisulphite sequencing approach. We collected and curated clinical data on 200 newborn infants; whose umbilical cord blood samples were analysed with the reduced representation bisulphite sequencing (RRBS) method. A generalized linear mixed-effects model was fit for each high coverage CpG site, followed by spatial and multiple testing adjustment of P values to identify differentially methylated cytosines (DMCs) and regions (DMRs) associated with clinical variables, such as maternal age, mode of delivery, and birth weight. Type 1 error rate was then evaluated with a permutation analysis. We discovered a strong inflation of spatially adjusted P values through the permutation analysis, which we then applied for empirical type 1 error control. The inflation of P values was caused by a common method for spatial adjustment and DMR detection, implemented in tools comb-p and RADMeth. Based on empirically estimated significance thresholds, very little differential methylation was associated with any of the studied clinical variables, other than sex. With this analysis workflow, the sex-associated differentially methylated regions were highly reproducible across studies, technologies, and statistical models.Peer reviewe

A Placebo-controlled double-blinded test of the biodiversity hypothesis of immune-mediated diseases : Environmental microbial diversity elicits changes in cytokines and increase in T regulatory cells in young children

Background: According to the biodiversity hypothesis of immune-mediated diseases, lack of microbiological di-versity in the everyday living environment is a core reason for dysregulation of immune tolerance and - even-tually - the epidemic of immune-mediated diseases in western urban populations. Despite years of intense research, the hypothesis was never tested in a double-blinded and placebo-controlled intervention trial.Objective: We aimed to perform the first placebo-controlled double-blinded test that investigates the effect of biodiversity on immune tolerance. Methods: In the intervention group, children aged 3-5 years were exposed to playground sand enriched with microbially diverse soil, or in the placebo group, visually similar, but microbially poor sand colored with peat (13 participants per treatment group). Children played twice a day for 20 min in the sandbox for 14 days. Sand, skin and gut bacterial, and blood samples were taken at baseline and after 14 days. Bacterial changes were followed for 28 days. Sand, skin and gut metagenome was determined by high throughput sequencing of bacterial 16 S rRNA gene. Cytokines were measured from plasma and the frequency of blood regulatory T cells was defined as a percentage of total CD3 +CD4 + T cells. Results: Bacterial richness (P < 0.001) and diversity (P < 0.05) were higher in the intervention than placebo sand. Skin bacterial community, including Gammaproteobacteria, shifted only in the intervention treatment to resemble the bacterial community in the enriched sand (P < 0.01). Mean change in plasma interleukin-10 (IL-10) concentration and IL-10 to IL-17A ratio supported immunoregulation in the intervention treatment compared to the placebo treatment (P = 0.02). IL-10 levels (P = 0.001) and IL-10 to IL-17A ratio (P = 0.02) were associated with Gammaproteobacterial community on the skin. The change in Treg frequencies was associated with the relative abundance of skin Thermoactinomycetaceae 1 (P = 0.002) and unclassified Alphaproteobacteria (P < 0.001). After 28 days, skin bacterial community still differed in the intervention treatment compared to baseline (P < 0.02). Conclusions: This is the first double-blinded placebo-controlled study to show that daily exposure to microbial biodiversity is associated with immune modulation in humans. The findings support the biodiversity hypothesis of immune-mediated diseases. We conclude that environmental microbiota may contribute to child health, and that adding microbiological diversity to everyday living environment may support immunoregulation.Peer reviewe

Macroscopic appearance of the major duodenal papilla influences bile duct cannulation: a prospective multicenter study by the Scandinavian Association for Digestive Endoscopy Study Group for ERCP

Background and AimsCertain appearances of the major duodenal papilla have been claimed to make cannulation more difficult during ERCP. This study uses a validated classification of the endoscopic appearance of the major duodenal papilla to determine if certain types of papilla predispose to difficult cannulation.MethodsPatients with a naïve papilla scheduled for ERCP were included. The papilla was classified into 1 of 4 papilla types before cannulation started. Time to successful bile duct cannulation, attempts, and number of pancreatic duct passages were recorded. Difficult cannulation was defined as after 5 minutes, 5 attempts, or 2 pancreatic guidewire passages.ResultsA total of 1401 patients were included from 9 different centers in the Nordic countries. The overall frequency of difficult cannulation was 42% (95% confidence interval [CI], 39%-44%). Type 2 small papilla (52%; 95% CI, 45%-59%) and type 3 protruding or pendulous papilla (48%; 95% CI, 42%-53%) were more frequently difficult to cannulate compared with type 1 regular papilla (36%; 95% CI, 33%-40%; both P P ConclusionsThe endoscopic appearance of the major duodenal papilla influences bile duct cannulation. Small type 2 and protruding or pendulous type 3 papillae are more frequently difficult to cannulate. In addition, cannulation might even fail more frequently if a beginner starts cannulation. These findings should be taken into consideration when performing studies regarding bile duct cannulation and in training future generations of endoscopists.</div